1-27547470-G-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001371928.1(AHDC1):c.4646C>A(p.Ser1549Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000438 in 1,598,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000044 ( 0 hom. )
Consequence
AHDC1
NM_001371928.1 missense
NM_001371928.1 missense
Scores
4
4
10
Clinical Significance
Conservation
PhyloP100: 4.83
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 Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.29995376).
BS2
?
High AC in GnomAd at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AHDC1 | NM_001371928.1 | c.4646C>A | p.Ser1549Tyr | missense_variant | 8/9 | ENST00000673934.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AHDC1 | ENST00000673934.1 | c.4646C>A | p.Ser1549Tyr | missense_variant | 8/9 | NM_001371928.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152212Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000942 AC: 23AN: 244094Hom.: 0 AF XY: 0.0000907 AC XY: 12AN XY: 132242
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GnomAD4 exome AF: 0.0000443 AC: 64AN: 1446164Hom.: 0 Cov.: 30 AF XY: 0.0000419 AC XY: 30AN XY: 716514
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152212Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74352
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 23, 2022 | This variant has not been reported in the literature in individuals affected with AHDC1-related conditions. This variant is present in population databases (rs369828844, gnomAD 0.02%). This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 1549 of the AHDC1 protein (p.Ser1549Tyr). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;T;T;T
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;L;L
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.;N;.;.
REVEL
Benign
Sift
Pathogenic
D;.;D;.;.
Sift4G
Uncertain
D;.;D;.;.
Polyphen
D;D;D;D;D
Vest4
MutPred
Gain of catalytic residue at S1549 (P = 0.0071);Gain of catalytic residue at S1549 (P = 0.0071);Gain of catalytic residue at S1549 (P = 0.0071);Gain of catalytic residue at S1549 (P = 0.0071);Gain of catalytic residue at S1549 (P = 0.0071);
MVP
MPC
1.6
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