17-10628670-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_002470.4(MYH3):c.5806C>A(p.His1936Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH3 | NM_002470.4 | c.5806C>A | p.His1936Asn | missense_variant | Exon 41 of 41 | ENST00000583535.6 | NP_002461.2 | |
MYH3 | XM_011523870.4 | c.5806C>A | p.His1936Asn | missense_variant | Exon 41 of 41 | XP_011522172.1 | ||
MYH3 | XM_011523871.3 | c.5806C>A | p.His1936Asn | missense_variant | Exon 41 of 41 | XP_011522173.1 | ||
MYH3 | XM_047436127.1 | c.5806C>A | p.His1936Asn | 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.5806C>A | p.His1936Asn | missense_variant | Exon 41 of 41 | 5 | NM_002470.4 | ENSP00000464317.1 | ||
MYH3 | ENST00000577963.1 | n.348C>A | non_coding_transcript_exon_variant | Exon 2 of 2 | 2 | |||||
MYH3 | ENST00000579928.2 | n.336C>A | non_coding_transcript_exon_variant | Exon 3 of 3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249288Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134948
GnomAD4 exome Cov.: 30
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74348
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: MYH3 c.5806C>A (p.His1936Asn) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 249288 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.5806C>A in individuals affected with MYH3-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -
not provided Uncertain:1
This sequence change replaces histidine, which is basic and polar, with asparagine, which is neutral and polar, at codon 1936 of the MYH3 protein (p.His1936Asn). This variant is present in population databases (rs775287416, gnomAD 0.008%). 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%. 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