chr17-10529471-G-A
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 1P and 11B. PP3BP4_ModerateBP6BS1BS2
The NM_017534.6(MYH2):c.3128C>T(p.Ser1043Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000342 in 1,614,028 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_017534.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH2 | NM_017534.6 | c.3128C>T | p.Ser1043Phe | missense_variant | Exon 25 of 40 | ENST00000245503.10 | NP_060004.3 | |
MYH2 | NM_001100112.2 | c.3128C>T | p.Ser1043Phe | missense_variant | Exon 25 of 40 | NP_001093582.1 | ||
MYHAS | NR_125367.1 | n.168-38066G>A | intron_variant | Intron 2 of 10 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000263 AC: 40AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000625 AC: 157AN: 251352Hom.: 1 AF XY: 0.000596 AC XY: 81AN XY: 135848
GnomAD4 exome AF: 0.000350 AC: 512AN: 1461886Hom.: 3 Cov.: 34 AF XY: 0.000348 AC XY: 253AN XY: 727242
GnomAD4 genome AF: 0.000263 AC: 40AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74326
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: MYH2 c.3128C>T (p.Ser1043Phe) results in a non-conservative amino acid change located in the Myosin Tail domain (IPR002928) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00062 in 251352 control chromosomes in the gnomAD database, including 1 homozygotes. To our knowledge, no occurrence of c.3128C>T in individuals affected with Myopathy, Proximal, And Ophthalmoplegia and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 321678). Based on the evidence outlined above, the variant was classified as uncertain significance. -
Inclusion Body Myopathy, Dominant Uncertain:1
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Myopathy, proximal, and ophthalmoplegia Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at