Variant: NM_194248.3(OTOF):c.5405C>T (p.Ala1802Val)

CA1562832

897955 (ClinVar)

Gene: OTOF

Condition: nonsyndromic genetic deafness

Inheritance Mode: Autosomal recessive inheritance

UUID: 37988287-c3c7-4c5c-902d-0a080e47563e

HGVS expressions

NM_194248.3:c.5405C>T
NM_194248.3(OTOF):c.5405C>T (p.Ala1802Val)
NC_000002.12:g.26461824G>A
CM000664.2:g.26461824G>A
NC_000002.11:g.26684692G>A
CM000664.1:g.26684692G>A
NC_000002.10:g.26538196G>A
NG_009937.1:g.101875C>T
ENST00000272371.7:c.5405C>T
ENST00000339598.8:c.3104C>T
ENST00000402415.8:c.3164C>T
ENST00000272371.6:c.5405C>T
ENST00000338581.10:c.3104C>T
ENST00000339598.7:c.3104C>T
ENST00000402415.7:c.3335C>T
ENST00000403946.7:c.5405C>T
NM_001287489.1:c.5405C>T
NM_004802.3:c.3104C>T
NM_194248.2:c.5405C>T
NM_194322.2:c.3335C>T
NM_194323.2:c.3104C>T
NM_001287489.2:c.5405C>T
NM_004802.4:c.3104C>T
NM_194322.3:c.3335C>T
NM_194323.3:c.3104C>T

Uncertain Significance

• Met criteria codes: PP3

• Not Met criteria codes: BA1 PP4 PM3 PM2

Expert Panel

Hearing Loss VCEP

Criteria Specification Information

Evidence submitted by expert panel

Hearing Loss VCEP

The REVEL computational prediction analysis tool produced a score of 0.729 for the c.5405C>T (p.Ala1802Val) variant in OTOF, which is above the threshold necessary to apply PP3, and the amino acid residue is well conserved in UCSC (PP3). This variant has been detected in 3 patients with hearing loss. For 2 of those patients, this variant was observed compound heterozygous with rare but unknown variants, and in 1 the variant was observed in the heterozygous state along with heterozygous variants in other hearing loss related genes. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: PP3.

Met criteria codes

• PP3: REVEL score of 0.729, which is greater than the HL VCEP threshold of 0.7. Amino acid residue is well conserved in UCSC.

Not Met criteria codes

• BA1: Present in 0.05012% (10/19952) of East Asian alleles in gnomAD. ExAC FAF: 0.019%
• PP4: Neither of the 2 patients compound heterozygous for this variant had ANSD.
• PM3: Detected in trans with c.3205T>G (p.F1069V) in one patient with severe HL and in trans with c.650A>G (p.D217G) in one patient with mild HL. Both trans variants are rare, but phase is unknown (0 PM3 points).
• PM2: Greater than 0.007%

Approved on: 2021-06-16

Published on: 2022-05-13