Variant: NM_005422.2(TECTA):c.487-7C>G

CA6326508

229304 (ClinVar)

Gene: TECTA

Condition: nonsyndromic genetic deafness

Inheritance Mode: Autosomal dominant inheritance

UUID: d7212d61-7f7d-4c9d-a9e0-bca3b51a0bd7

HGVS expressions

NM_005422.2:c.487-7C>G
NM_005422.2(TECTA):c.487-7C>G
NM_005422.2:n.487-7C>G
ENST00000264037.2:n.487-7C>G
ENST00000392793.5:c.487-7C>G
NC_000011.10:g.121113065C>G
CM000673.2:g.121113065C>G
NC_000011.9:g.120983774C>G
CM000673.1:g.120983774C>G
NC_000011.8:g.120488984C>G
NG_011633.1:g.15400C>G

Likely Benign

• Met criteria codes: BP7 BP4

• Not Met criteria codes: BA1 BS1 BP5 PS4

Expert Panel

Hearing Loss VCEP

Criteria Specification Information

Evidence submitted by expert panel

Hearing Loss VCEP

The c.487-7C>G intronic variant in TECTA was present in 0.05081% (18/35428) of Latino alleles in gnomAD; however, because this gene has been associated with both AR and AD hearing loss, no criteria were applied based on population data. This variant was identified in 1 white patient with nonsyndromic hearing loss (PS4 not met; Laboratory for Molecular Medicine internal data, SCV000272492.3). The c.487-7C>G variant is classified as likely benign because a C>G change at this position does not diverge from the splice consensus sequence, making it unlikely to impact splicing, and computational splice prediction tools do not predict an impact on splicing. ACMG/AMP Criteria applied, as specified by the Hearing Loss Expert Panel: BP4, BP7.

Met criteria codes

• BP7: Intronic variant with no impact to splicing at a site that is not highly conserved.
• BP4: Splicing is not predicted to be impacted. Site is not highly conserved (15 different mammals in UCSC database have mutations at this nucleotide, 1 is G specifically). REVEL score not available, but CADD score = 0.967818 (impact threshold is 19).

Not Met criteria codes

• BA1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS1: Present in 0.05081% (18/35428) of Latino alleles in gnomAD.
• BP5: Other causes of disease are due to recessive genes.
• PS4: LMM internal data: previously identified in one infant white male with mild-moderate SNHL who also had a VUS in MYO3A and a pathogenic variant in SLC26A4. Also identified in 2 other individuals: 1 2yo male with progressive profound SNHL with EVA. However, this individual had 2 pathogenic variants in SLC26A4 (along with VUS variants in LOXHD1, MYO6, MYO7A, USH2A, and another TECTA). Also seen in 1 other 2yo male with SNHL homozygous for the 169G>T variant in OTOF (not in ClinVar, but predicted by Almontashiri et al. (PMID: 29048421) to be pathogenic). Also had VUS variants in BSND, CDH23, and TRIOBP. With only 1 proband without an alternative mechanism for disease, PS4_Supporting not met.

Approved on: 2019-10-02

Published on: 2019-10-02