Variant 18-9254513-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015208.5(ANKRD12):c.1246C>A(p.Gln416Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000151 in 1,387,452 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: not found (cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

ANKRD12
NM_015208.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.63

Variant links:

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]

ANKRD12 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27208805).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD12	NM_015208.5 linkuse as main transcript	c.1246C>A	p.Gln416Lys	missense_variant	9/13	ENST00000262126.9	NP_056023.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD12	ENST00000262126.9 linkuse as main transcript	c.1246C>A	p.Gln416Lys	missense_variant	9/13	1	NM_015208.5	ENSP00000262126	P4	Q6UB98-1
ANKRD12	ENST00000400020.7 linkuse as main transcript	c.1177C>A	p.Gln393Lys	missense_variant	8/12	1		ENSP00000382897	A2	Q6UB98-2
ANKRD12	ENST00000359158.7 linkuse as main transcript	c.*360C>A		3_prime_UTR_variant, NMD_transcript_variant	4/4	2		ENSP00000352073

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1387452

Hom.:

Cov.:

AF XY:

0.0000117

AC XY:

AN XY:

686318

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000185

Gnomad4 OTH exome

AF:

0.0000176

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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 19, 2022

The c.1246C>A (p.Q416K) alteration is located in exon 9 (coding exon 8) of the ANKRD12 gene. This alteration results from a C to A substitution at nucleotide position 1246, causing the glutamine (Q) at amino acid position 416 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.027

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0085

T;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

0.10

N;.

REVEL

Benign

0.20

Sift

Benign

0.033

D;.

Sift4G

Benign

1.0

T;T

Polyphen

0.99

D;D

Vest4

0.43

MutPred

0.29

Gain of methylation at Q416 (P = 0.0087);.;

MVP

0.30

ClinPred

0.34

GERP RS

5.9

Varity_R

0.12

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over