Variant 18-9254837-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015208.5(ANKRD12):c.1570T>A(p.Ser524Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 1,336,770 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ANKRD12
NM_015208.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD12	NM_015208.5 linkuse as main transcript	c.1570T>A	p.Ser524Thr	missense_variant	9/13	ENST00000262126.9	NP_056023.3	Q6UB98-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ANKRD12	ENST00000262126.9 linkuse as main transcript	c.1570T>A	p.Ser524Thr	missense_variant	9/13	1	NM_015208.5	ENSP00000262126.3	Q6UB98-1
ANKRD12	ENST00000400020.7 linkuse as main transcript	c.1501T>A	p.Ser501Thr	missense_variant	8/12	1		ENSP00000382897.3	Q6UB98-2
ANKRD12	ENST00000359158.7 linkuse as main transcript	n.*684T>A		non_coding_transcript_exon_variant	4/4	2		ENSP00000352073.7	B5MEA4
ANKRD12	ENST00000359158.7 linkuse as main transcript	n.*684T>A		3_prime_UTR_variant	4/4	2		ENSP00000352073.7	B5MEA4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000120

AC:

AN:

1336770

Hom.:

Cov.:

AF XY:

0.00000916

AC XY:

AN XY:

655226

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:

0.0000152

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 21, 2022

The c.1570T>A (p.S524T) alteration is located in exon 9 (coding exon 8) of the ANKRD12 gene. This alteration results from a T to A substitution at nucleotide position 1570, causing the serine (S) at amino acid position 524 to be replaced by a threonine (T). 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

0.10

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.057

T;.

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.81

T;T

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.51

D;D

MetaSVM

Uncertain

0.77

MutationAssessor

Uncertain

2.1

M;.

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.9

N;.

REVEL

Uncertain

0.48

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.11

T;T

Polyphen

1.0

D;D

Vest4

0.49

MutPred

0.12

Gain of glycosylation at S524 (P = 0.0299);.;

MVP

0.91

ClinPred

0.88

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.51

gMVP

0.085

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over