1-27547429-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_001371928.1(AHDC1):c.4687G>A(p.Ala1563Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000145 in 1,583,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001371928.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AHDC1 | NM_001371928.1 | c.4687G>A | p.Ala1563Thr | missense_variant | Exon 8 of 9 | ENST00000673934.1 | NP_001358857.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152228Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000212 AC: 5AN: 235554Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 126940
GnomAD4 exome AF: 0.0000147 AC: 21AN: 1431520Hom.: 0 Cov.: 30 AF XY: 0.0000184 AC XY: 13AN XY: 707078
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152346Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74494
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1563 of the AHDC1 protein (p.Ala1563Thr). This variant is present in population databases (rs539447084, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with AHDC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1463597). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Possibly Damaging". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. -
Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at