17-10628676-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBS2_Supporting
The NM_002470.4(MYH3):c.5800G>A(p.Val1934Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,870 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_002470.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH3 | NM_002470.4 | c.5800G>A | p.Val1934Met | missense_variant | Exon 41 of 41 | ENST00000583535.6 | NP_002461.2 | |
MYH3 | XM_011523870.4 | c.5800G>A | p.Val1934Met | missense_variant | Exon 41 of 41 | XP_011522172.1 | ||
MYH3 | XM_011523871.3 | c.5800G>A | p.Val1934Met | missense_variant | Exon 41 of 41 | XP_011522173.1 | ||
MYH3 | XM_047436127.1 | c.5800G>A | p.Val1934Met | missense_variant | Exon 43 of 43 | XP_047292083.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH3 | ENST00000583535.6 | c.5800G>A | p.Val1934Met | missense_variant | Exon 41 of 41 | 5 | NM_002470.4 | ENSP00000464317.1 | ||
MYH3 | ENST00000577963.1 | n.342G>A | non_coding_transcript_exon_variant | Exon 2 of 2 | 2 | |||||
MYH3 | ENST00000579928.2 | n.330G>A | non_coding_transcript_exon_variant | Exon 3 of 3 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249212Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134908
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461870Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5AN XY: 727240
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1934 of the MYH3 protein (p.Val1934Met). This variant is present in population databases (rs770223770, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MYH3-related conditions. ClinVar contains an entry for this variant (Variation ID: 2061705). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt MYH3 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at