rs771154512
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_017433.5(MYO3A):c.2168A>G(p.Asn723Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,612,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. N723H) has been classified as Uncertain significance.
Frequency
Consequence
NM_017433.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO3A | NM_017433.5 | c.2168A>G | p.Asn723Ser | missense_variant | 20/35 | ENST00000642920.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO3A | ENST00000642920.2 | c.2168A>G | p.Asn723Ser | missense_variant | 20/35 | NM_017433.5 | P1 | ||
MYO3A | ENST00000543632.5 | c.1776+31762A>G | intron_variant | 1 | |||||
MYO3A | ENST00000642197.1 | n.2372A>G | non_coding_transcript_exon_variant | 20/27 | |||||
MYO3A | ENST00000647478.1 | c.*163A>G | 3_prime_UTR_variant, NMD_transcript_variant | 18/30 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1460634Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 6AN XY: 726720
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74324
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 16, 2018 | The p.Asn723Ser variant in MYO3A has not been previously reported in individuals with hearing loss. It has been identified in 1/66566 European chromosomes by th e Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs77 1154512); however, its frequency is not high enough to rule out a pathogenic rol e. Computational prediction tools and conservation analysis suggest that the p.A sn723Ser variant may impact the protein, though this information is not predicti ve enough to determine pathogenicity. In summary, the clinical significance of t he p.Asn723Ser variant is uncertain. ACMG/AMP Criteria applied: PP3, PM2. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at