rs780020430
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_002476.2(MYL4):c.113C>A(p.Ala38Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,614,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A38G) has been classified as Uncertain significance.
Frequency
Consequence
NM_002476.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYL4 | NM_002476.2 | c.113C>A | p.Ala38Asp | missense_variant | 1/7 | ENST00000393450.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYL4 | ENST00000393450.5 | c.113C>A | p.Ala38Asp | missense_variant | 1/7 | 1 | NM_002476.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152210Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251230Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135812
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461882Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727246
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74352
ClinVar
Submissions by phenotype
Atrial fibrillation, familial, 18 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2023 | 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 missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 542789). This variant has not been reported in the literature in individuals affected with MYL4-related conditions. This variant is present in population databases (rs780020430, gnomAD 0.009%). This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 38 of the MYL4 protein (p.Ala38Asp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at