Variant: NM_000260.4(MYO7A):c.19G>A (p.Gly7Arg)

CA6197006

802700 (ClinVar)

Gene: MYO7A

Condition: nonsyndromic genetic deafness

Inheritance Mode: Autosomal recessive inheritance

UUID: bce470f8-6cff-46e7-813f-f8d6bc816152

HGVS expressions

NM_000260.4:c.19G>A
NM_000260.4(MYO7A):c.19G>A (p.Gly7Arg)
NM_000260.3:c.19G>A
NM_001127179.2:c.19G>A
NM_001127180.1:c.19G>A
NM_001127180.2:c.19G>A
NM_001369365.1:c.-15G>A
ENST00000409619.6:c.-15G>A
ENST00000409709.7:c.19G>A
ENST00000409893.5:c.19G>A
ENST00000458637.6:c.19G>A
ENST00000620575.4:c.19G>A
NC_000011.10:g.77142709G>A
CM000673.2:g.77142709G>A
NC_000011.9:g.76853755G>A
CM000673.1:g.76853755G>A
NC_000011.8:g.76531403G>A
NG_009086.1:g.19446G>A
NG_009086.2:g.19464G>A

Uncertain Significance

• Met criteria codes: PP3 BS1_Supporting

Expert Panel

Hearing Loss VCEP

Criteria Specification Information

Evidence submitted by expert panel

Hearing Loss VCEP

The filtering allele frequency (the lower threshold of the 95% CI of 56/42008) of the c.19G>A (p.Gly7Arg) variant in the MYO7A gene is 0.102% for African chromosomes by gnomAD v3, which is a higher frequency than would be expected for an autosomal recessive pathogenic variant based on the thresholds defined by the ClinGen Hearing Loss Expert Panel (BS1_Supporting). The REVEL computational prediction tool produced a score of 0.926, which is above the threshold necessary to apply PP3. In summary, the clinical significance of the p.Thr67Ser variant is uncertain. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BS1_Supporting, PP3.

Met criteria codes

• PP3: REVEL score is 0.926 and residue is conserved across all vertebrates in UCSC.
• BS1_Supporting: Present in 0.102% (37/23276) of African chromosomes in gnomAD v2.1.1 and in 0.105% (56/42008) of African chromosomes in gnomAD v3 (both popmax filtering AF, 95% CI).

Approved on: 2020-12-24

Published on: 2020-12-24