rs786205461
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_014391.3(ANKRD1):c.790C>T(p.Arg264Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R264H) 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 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANKRD1 | NM_014391.3 | c.790C>T | p.Arg264Cys | missense_variant | 8/9 | ENST00000371697.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANKRD1 | ENST00000371697.4 | c.790C>T | p.Arg264Cys | missense_variant | 8/9 | 1 | NM_014391.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152056Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251024Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135658
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461778Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727198
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152056Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 74250
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Department Of Translational Genomics (developmental Genetics Section), King Faisal Specialist Hospital & Research Centre | - | - - |
ANKRD1-related dilated cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 25, 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ANKRD1 protein function. ClinVar contains an entry for this variant (Variation ID: 191008). This variant has not been reported in the literature in individuals affected with ANKRD1-related conditions. This variant is present in population databases (rs786205461, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 264 of the ANKRD1 protein (p.Arg264Cys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at