rs199719452
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001371928.1(AHDC1):c.212C>T(p.Thr71Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00586 in 1,593,968 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0041 ( 3 hom., cov: 31)
Exomes 𝑓: 0.0060 ( 31 hom. )
Consequence
AHDC1
NM_001371928.1 missense
NM_001371928.1 missense
Scores
1
5
12
Clinical Significance
Conservation
PhyloP100: 3.65
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.006389588).
BP6
?
Variant 1-27551904-G-A is Benign according to our data. Variant chr1-27551904-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 377378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00411 (623/151440) while in subpopulation NFE AF= 0.00673 (456/67738). AF 95% confidence interval is 0.00622. There are 3 homozygotes in gnomad4. There are 284 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 623 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AHDC1 | NM_001371928.1 | c.212C>T | p.Thr71Ile | missense_variant | 8/9 | ENST00000673934.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AHDC1 | ENST00000673934.1 | c.212C>T | p.Thr71Ile | missense_variant | 8/9 | NM_001371928.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00410 AC: 621AN: 151326Hom.: 3 Cov.: 31
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GnomAD3 exomes AF: 0.00383 AC: 873AN: 228156Hom.: 3 AF XY: 0.00375 AC XY: 469AN XY: 125142
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GnomAD4 exome AF: 0.00605 AC: 8721AN: 1442528Hom.: 31 Cov.: 49 AF XY: 0.00587 AC XY: 4195AN XY: 715244
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GnomAD4 genome ? AF: 0.00411 AC: 623AN: 151440Hom.: 3 Cov.: 31 AF XY: 0.00384 AC XY: 284AN XY: 73990
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Asia WGS
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 03, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Aug 19, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | AHDC1: BS1, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 30, 2019 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 01, 2021 | 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. - |
AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;N;N
MutationTaster
Benign
N;N
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.;N;.;.
REVEL
Benign
Sift
Uncertain
D;.;D;.;.
Sift4G
Uncertain
D;.;D;.;.
Polyphen
B;B;B;B;B
Vest4
MVP
MPC
1.3
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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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