rs1165205177
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001371928.1(AHDC1):c.2062C>T(p.Arg688Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,868 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 Pathogenic (★★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
AHDC1
NM_001371928.1 stop_gained
NM_001371928.1 stop_gained
Scores
3
3
1
Clinical Significance
Conservation
PhyloP100: 2.62
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 48 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-27550054-G-A is Pathogenic according to our data. Variant chr1-27550054-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 438276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-27550054-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AHDC1 | NM_001371928.1 | c.2062C>T | p.Arg688Ter | stop_gained | 8/9 | ENST00000673934.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AHDC1 | ENST00000673934.1 | c.2062C>T | p.Arg688Ter | stop_gained | 8/9 | NM_001371928.1 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 6.88e-7 AC: 1AN: 1452868Hom.: 0 Cov.: 62 AF XY: 0.00000139 AC XY: 1AN XY: 721544
GnomAD4 exome
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AC:
1
AN:
1452868
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Cov.:
62
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AC XY:
1
AN XY:
721544
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome Pathogenic:5
Pathogenic, criteria provided, single submitter | clinical testing | Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille | - | - - |
Pathogenic, no assertion criteria provided | clinical testing | Pediatric Genetics Clinic, Sheba Medical Center | May 13, 2021 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine | - | - - |
Likely pathogenic, no assertion criteria provided | clinical testing | Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals | Mar 23, 2016 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Equipe Genetique des Anomalies du Developpement, Université de Bourgogne | Jan 01, 2016 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2023 | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 438276). This premature translational stop signal has been observed in individual(s) with Xia-Gibbs syndrome (PMID: 29696776). This sequence change creates a premature translational stop signal (p.Arg688*) in the AHDC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AHDC1 are known to be pathogenic (PMID: 24791903, 27148574). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at