chr18-9208671-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015208.5(ANKRD12):āc.319G>Cā(p.Glu107Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000305 in 1,607,250 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 (ā ).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 32)
Exomes š: 0.000031 ( 0 hom. )
Consequence
ANKRD12
NM_015208.5 missense
NM_015208.5 missense
Scores
3
6
10
Clinical Significance
Conservation
PhyloP100: 10.0
Genes affected
ANKRD12 (HGNC:29135): (ankyrin repeat domain 12) This gene encodes a member of the ankyrin repeats-containing cofactor family. These proteins may inhibit the transcriptional activity of nuclear receptors through the recruitment of histone deacetylases. The encoded protein interacts with p160 coactivators and also represses transcription mediated by the coactivator alteration/deficiency in activation 3 (ADA3). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18139732).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ANKRD12 | NM_015208.5 | c.319G>C | p.Glu107Gln | missense_variant | 5/13 | ENST00000262126.9 | NP_056023.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ANKRD12 | ENST00000262126.9 | c.319G>C | p.Glu107Gln | missense_variant | 5/13 | 1 | NM_015208.5 | ENSP00000262126 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 151998Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000650 AC: 16AN: 246176Hom.: 0 AF XY: 0.0000752 AC XY: 10AN XY: 132896
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GnomAD4 exome AF: 0.0000309 AC: 45AN: 1455252Hom.: 0 Cov.: 30 AF XY: 0.0000332 AC XY: 24AN XY: 723564
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 151998Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74236
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 13, 2023 | The c.319G>C (p.E107Q) alteration is located in exon 5 (coding exon 4) of the ANKRD12 gene. This alteration results from a G to C substitution at nucleotide position 319, causing the glutamic acid (E) at amino acid position 107 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;D
REVEL
Benign
Sift
Uncertain
D;.;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;.
Vest4
MVP
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