12-57036315-T-C
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_005379.4(MYO1A):āc.2341A>Gā(p.Lys781Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,613,606 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_005379.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO1A | NM_005379.4 | c.2341A>G | p.Lys781Glu | missense_variant | 22/28 | ENST00000300119.8 | |
MYO1A | NM_001256041.2 | c.2341A>G | p.Lys781Glu | missense_variant | 23/29 | ||
MYO1A | XM_047428876.1 | c.2341A>G | p.Lys781Glu | missense_variant | 23/29 | ||
MYO1A | XM_011538373.3 | c.2341A>G | p.Lys781Glu | missense_variant | 22/25 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO1A | ENST00000300119.8 | c.2341A>G | p.Lys781Glu | missense_variant | 22/28 | 1 | NM_005379.4 | P1 | |
MYO1A | ENST00000442789.6 | c.2341A>G | p.Lys781Glu | missense_variant | 23/29 | 1 | P1 | ||
MYO1A | ENST00000554234.5 | c.1855A>G | p.Lys619Glu | missense_variant, NMD_transcript_variant | 18/24 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00101 AC: 153AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000796 AC: 200AN: 251146Hom.: 0 AF XY: 0.000884 AC XY: 120AN XY: 135716
GnomAD4 exome AF: 0.00141 AC: 2057AN: 1461446Hom.: 4 Cov.: 32 AF XY: 0.00134 AC XY: 976AN XY: 727030
GnomAD4 genome AF: 0.00101 AC: 153AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.00106 AC XY: 79AN XY: 74330
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:3
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 02, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 18, 2021 | The c.2341A>G (p.K781E) alteration is located in exon 22 (coding exon 21) of the MYO1A gene. This alteration results from a A to G substitution at nucleotide position 2341, causing the lysine (K) at amino acid position 781 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 01, 2014 | Lys781Glu in exon 22 of MYO1A: This variant is not expected to have clinical sig nificance because it has been identified in 0.23% (20/8600) of European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu ; dbSNP rs144384395). In addition, lysine (Lys) is not well conserved in mammals and across evolutionary distant species, and several computational prediction t ools suggest this variant may not impact the protein. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at