rs34165480
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP6BS2
The NM_002470.4(MYH3):c.4910C>T(p.Ala1637Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00458 in 1,614,084 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A1637A) has been classified as Likely benign.
Frequency
Consequence
NM_002470.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH3 | NM_002470.4 | c.4910C>T | p.Ala1637Val | missense_variant | 34/41 | ENST00000583535.6 | |
LOC124903927 | XR_007065620.1 | n.221+758G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH3 | ENST00000583535.6 | c.4910C>T | p.Ala1637Val | missense_variant | 34/41 | 5 | NM_002470.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00307 AC: 467AN: 152190Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00311 AC: 781AN: 251002Hom.: 5 AF XY: 0.00294 AC XY: 399AN XY: 135734
GnomAD4 exome AF: 0.00474 AC: 6924AN: 1461776Hom.: 30 Cov.: 51 AF XY: 0.00457 AC XY: 3323AN XY: 727196
GnomAD4 genome AF: 0.00307 AC: 467AN: 152308Hom.: 2 Cov.: 32 AF XY: 0.00291 AC XY: 217AN XY: 74470
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | MYH3: BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 16, 2021 | This variant is associated with the following publications: (PMID: 29687901, 30487145, 25957469, 16642020) - |
Freeman-Sheldon syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 03, 2017 | - - |
MYH3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 23, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Distal arthrogryposis type 2B1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at