17-10628661-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_002470.4(MYH3):c.5815G>A(p.Glu1939Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,614,216 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 Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH3 | NM_002470.4 | c.5815G>A | p.Glu1939Lys | missense_variant | Exon 41 of 41 | ENST00000583535.6 | NP_002461.2 | |
MYH3 | XM_011523870.4 | c.5815G>A | p.Glu1939Lys | missense_variant | Exon 41 of 41 | XP_011522172.1 | ||
MYH3 | XM_011523871.3 | c.5815G>A | p.Glu1939Lys | missense_variant | Exon 41 of 41 | XP_011522173.1 | ||
MYH3 | XM_047436127.1 | c.5815G>A | p.Glu1939Lys | 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.5815G>A | p.Glu1939Lys | missense_variant | Exon 41 of 41 | 5 | NM_002470.4 | ENSP00000464317.1 | ||
MYH3 | ENST00000577963.1 | n.357G>A | non_coding_transcript_exon_variant | Exon 2 of 2 | 2 | |||||
MYH3 | ENST00000579928.2 | n.345G>A | non_coding_transcript_exon_variant | Exon 3 of 3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249386Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134978
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461886Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727244
GnomAD4 genome AF: 0.00000656 AC: 1AN: 152330Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74502
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1939 of the MYH3 protein (p.Glu1939Lys). This variant is present in population databases (rs555639778, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MYH3-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MYH3 protein function with a negative predictive value of 95%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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