chr17-10400593-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_002472.3(MYH8):c.3532C>T(p.Arg1178Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000545 in 1,614,074 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_002472.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH8 | ENST00000403437.2 | c.3532C>T | p.Arg1178Cys | missense_variant | Exon 27 of 40 | 5 | NM_002472.3 | ENSP00000384330.2 | ||
ENSG00000272736 | ENST00000399342.6 | n.77-5555G>A | intron_variant | Intron 1 of 3 | 3 | |||||
ENSG00000272736 | ENST00000581304.1 | n.53-5555G>A | intron_variant | Intron 1 of 3 | 3 | |||||
MYHAS | ENST00000587182.2 | n.65-5555G>A | intron_variant | Intron 1 of 10 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000637 AC: 97AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000986 AC: 248AN: 251486Hom.: 1 AF XY: 0.000920 AC XY: 125AN XY: 135918
GnomAD4 exome AF: 0.000535 AC: 782AN: 1461892Hom.: 4 Cov.: 32 AF XY: 0.000549 AC XY: 399AN XY: 727246
GnomAD4 genome AF: 0.000637 AC: 97AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.000605 AC XY: 45AN XY: 74336
ClinVar
Submissions by phenotype
not specified Uncertain:1
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Hecht syndrome Uncertain:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
MYH8-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at