19-50210403-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001145809.2(MYH14):c.38C>T(p.Ala13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000761 in 1,576,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001145809.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH14 | NM_001145809.2 | c.38C>T | p.Ala13Val | missense_variant | 2/43 | ENST00000642316.2 | NP_001139281.1 | |
MYH14 | NM_001077186.2 | c.38C>T | p.Ala13Val | missense_variant | 2/42 | NP_001070654.1 | ||
MYH14 | NM_024729.4 | c.38C>T | p.Ala13Val | missense_variant | 2/41 | NP_079005.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH14 | ENST00000642316.2 | c.38C>T | p.Ala13Val | missense_variant | 2/43 | NM_001145809.2 | ENSP00000493594 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152144Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000702 AC: 10AN: 1424008Hom.: 0 Cov.: 31 AF XY: 0.0000113 AC XY: 8AN XY: 706338
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74316
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 13, 2022 | This variant has not been reported in the literature in individuals affected with MYH14-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 expected to disrupt MYH14 protein function. ClinVar contains an entry for this variant (Variation ID: 1412598). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 13 of the MYH14 protein (p.Ala13Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at