chr14-23417617-C-T
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000257.4(MYH7):c.4239G>A(p.Ser1413Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00189 in 1,612,902 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000257.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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MYH7 | NM_000257.4 | c.4239G>A | p.Ser1413Ser | synonymous_variant | Exon 31 of 40 | ENST00000355349.4 | NP_000248.2 | |
MYH7 | NM_001407004.1 | c.4239G>A | p.Ser1413Ser | synonymous_variant | Exon 30 of 39 | NP_001393933.1 | ||
MHRT | NR_126491.1 | n.*22C>T | downstream_gene_variant |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00267 AC: 407AN: 152206Hom.: 2 Cov.: 33
GnomAD3 exomes AF: 0.00348 AC: 876AN: 251480Hom.: 10 AF XY: 0.00346 AC XY: 470AN XY: 135916
GnomAD4 exome AF: 0.00181 AC: 2647AN: 1460578Hom.: 34 Cov.: 34 AF XY: 0.00181 AC XY: 1317AN XY: 726588
GnomAD4 genome AF: 0.00268 AC: 408AN: 152324Hom.: 2 Cov.: 33 AF XY: 0.00400 AC XY: 298AN XY: 74486
ClinVar
Submissions by phenotype
not specified Benign:6
p.Ser1413Ser in exon 31 of MYH7: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 4/8600 European A merican chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washing ton.edu/EVS/; dbSNP rs3729821). -
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. -
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not provided Benign:5
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MYH7: BP4, BP7, BS2 -
Cardiomyopathy Benign:2
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Dilated cardiomyopathy 1S Benign:1
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. -
MYH7-related skeletal myopathy Benign:1
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. -
Myosin storage myopathy Benign:1
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. -
Congenital myopathy with fiber type disproportion;C1834481:Dilated cardiomyopathy 1S;C1842160:Myosin storage myopathy;C1850709:Myopathy, myosin storage, autosomal recessive;C3495498:Hypertrophic cardiomyopathy 1;C4552004:MYH7-related skeletal myopathy Benign:1
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Hypertrophic cardiomyopathy Benign:1
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Cardiovascular phenotype Benign:1
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Hypertrophic cardiomyopathy 1 Benign:1
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