chr17-8475904-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM1BP4_ModerateBS2
The NM_001256012.3(MYH10):c.5924G>A(p.Arg1975His) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,613,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001256012.3 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH10 | NM_001256012.3 | c.5924G>A | p.Arg1975His | missense_variant | Exon 43 of 43 | ENST00000360416.8 | NP_001242941.1 | |
MYH10 | NM_001375266.1 | c.5861G>A | p.Arg1954His | missense_variant | Exon 42 of 42 | NP_001362195.1 | ||
MYH10 | NM_001256095.2 | c.5858G>A | p.Arg1953His | missense_variant | Exon 42 of 42 | NP_001243024.1 | ||
MYH10 | NM_005964.5 | c.5831G>A | p.Arg1944His | missense_variant | Exon 41 of 41 | NP_005955.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152186Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251326Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135840
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461794Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727212
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152186Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74332
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.5831G>A (p.R1944H) alteration is located in exon 41 (coding exon 40) of the MYH10 gene. This alteration results from a G to A substitution at nucleotide position 5831, causing the arginine (R) at amino acid position 1944 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Jaw-winking syndrome Uncertain:1
The heterozygous p.Arg1975His variant in MYH10 was identified in 1 individual with isolated Marcus Gunn jaw-winking synkinesis with congenital ptosis via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Engle lab (https://kirbyneuro.org/EngleLab/). This variant was inherited from the mother of the proband who had isolated congenital ptosis without Marcus Gunn jaw-winking synkinesis. While this gene is still lacking sufficient evidence to establish a gene-disease association, we believe this is a possible novel gene candidate for Marcus Gunn jaw-winking syndrome. Given the limited information about this gene-disease relationship, the significance of the p.Arg1975His variant is uncertain. If you have any additional information about functional evidence or other individuals with this phenotype that also have variants in MYH10 we encourage you to reach out to the Engle Lab (elizabeth.engle@childrens.harvard.edu). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at