19-50230599-G-A
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001145809.2(MYH14):c.949G>A(p.Gly317Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,414,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G317A) has been classified as Uncertain significance.
Frequency
Consequence
NM_001145809.2 missense
Scores
Clinical Significance
Conservation
Publications
- autosomal dominant nonsyndromic hearing loss 4AInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
- peripheral neuropathy-myopathy-hoarseness-hearing loss syndromeInheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- nonsyndromic genetic hearing lossInheritance: AD Classification: MODERATE Submitted by: ClinGen
- autosomal dominant nonsyndromic hearing lossInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH14 | NM_001145809.2 | c.949G>A | p.Gly317Arg | missense_variant | Exon 9 of 43 | ENST00000642316.2 | NP_001139281.1 | |
MYH14 | NM_001077186.2 | c.949G>A | p.Gly317Arg | missense_variant | Exon 9 of 42 | NP_001070654.1 | ||
MYH14 | NM_024729.4 | c.925G>A | p.Gly309Arg | missense_variant | Exon 8 of 41 | NP_079005.3 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 7.07e-7 AC: 1AN: 1414164Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1AN XY: 698914 show subpopulations
Age Distribution
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
The Gly317Arg variant in MYH14 has not been reported in individuals with hearing loss. Data from large population studies are insufficient to assess the frequen cy of this variant. Computational analyses (biochemical amino acid properties, c onservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for o r against an impact to the protein. In summary, additional data is needed to det ermine the clinical significance of this variant. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at