chr1-27547398-G-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_001371928.1(AHDC1):c.4718C>T(p.Ala1573Val) variant causes a missense change. The variant allele was found at a frequency of 0.000044 in 1,568,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign 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. A1573S) has been classified as Likely benign.
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.4718C>T | p.Ala1573Val | missense_variant | Exon 8 of 9 | ENST00000673934.1 | NP_001358857.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000500 AC: 11AN: 220220Hom.: 0 AF XY: 0.0000422 AC XY: 5AN XY: 118478
GnomAD4 exome AF: 0.0000466 AC: 66AN: 1416718Hom.: 0 Cov.: 30 AF XY: 0.0000457 AC XY: 32AN XY: 699594
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74370
ClinVar
Submissions by phenotype
AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Neuberg Centre For Genomic Medicine, NCGM | May 20, 2023 | The observed missense variant c.4718C>T(p.Ala1573Val) in AHDC1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.4718C>T variant has 0.005% allele frequency in gnomAD Exomes. This variant has been submitted to the ClinVar database as Uncertain Significance. However, no details are available for independent assessment.The amino acid Alanine at position 1573 is changed to a Valine changing protein sequence and it might alter its composition and physico-chemical properties. Computational evidence (Polyphe-Benign, SIFT-Damaging and Mutation Taster-polymorphism) predicts conflicting evidence on protein structure and function for this variant.The reference amino acid in AHDC1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 06, 2023 | 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 23, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at