rs777736953
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001371928.1(AHDC1):c.2773C>T(p.Arg925Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R925R) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
AHDC1
NM_001371928.1 stop_gained
NM_001371928.1 stop_gained
Scores
2
4
1
Clinical Significance
Conservation
PhyloP100: 0.939
Genes affected
AHDC1 (HGNC:25230): (AT-hook DNA binding motif containing 1) This gene encodes a protein containing two AT-hooks, which likely function in DNA binding. Mutations in this gene were found in individuals with Xia-Gibbs syndrome. [provided by RefSeq, Jun 2014]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 32 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-27549343-G-A is Pathogenic according to our data. Variant chr1-27549343-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 496678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AHDC1 | NM_001371928.1 | c.2773C>T | p.Arg925Ter | stop_gained | 8/9 | ENST00000673934.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AHDC1 | ENST00000673934.1 | c.2773C>T | p.Arg925Ter | stop_gained | 8/9 | NM_001371928.1 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1459490Hom.: 0 Cov.: 105 AF XY: 0.00 AC XY: 0AN XY: 725960
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
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0
AN:
1459490
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Cov.:
105
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0
AN XY:
725960
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ExAC
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AC:
1
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:5Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome Pathogenic:2Other:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 20, 2020 | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. - |
not provided, no classification provided | literature only | GeneReviews | - | Recurring pathogenic variant - |
Pathogenic, no assertion criteria provided | clinical testing | Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine | - | - - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen | Oct 23, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | May 28, 2019 | Observed de novo without confirmed parentage in multiple unrelated patients with features of Xia-Gibbs syndrome in published literature (Jiang et al., 2018); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016) - |
Abdominal obesity-metabolic syndrome 3 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Equipe Genetique des Anomalies du Developpement, Université de Bourgogne | Mar 31, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
GERP RS
Splicing
Name
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at