rs746392266
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014391.3(ANKRD1):c.944G>T(p.Arg315Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,542 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R315C) has been classified as Uncertain significance.
Frequency
Consequence
NM_014391.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANKRD1 | NM_014391.3 | c.944G>T | p.Arg315Leu | missense_variant | 9/9 | ENST00000371697.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANKRD1 | ENST00000371697.4 | c.944G>T | p.Arg315Leu | missense_variant | 9/9 | 1 | NM_014391.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250916Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135690
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461542Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727088
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
ANKRD1-related dilated cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 18, 2018 | This sequence change replaces arginine with leucine at codon 315 of the ANKRD1 protein (p.Arg315Leu). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is present in population databases (rs746392266, ExAC 0.003%). This variant has not been reported in the literature in individuals with ANKRD1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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