Variant 18-9254826-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015208.5(ANKRD12):c.1559A>G(p.Asn520Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000749 in 1,334,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

ANKRD12
NM_015208.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.370

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03458616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD12	NM_015208.5 linkuse as main transcript	c.1559A>G	p.Asn520Ser	missense_variant	9/13	ENST00000262126.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD12	ENST00000262126.9 linkuse as main transcript	c.1559A>G	p.Asn520Ser	missense_variant	9/13	1	NM_015208.5	P4	Q6UB98-1
ANKRD12	ENST00000400020.7 linkuse as main transcript	c.1490A>G	p.Asn497Ser	missense_variant	8/12	1		A2	Q6UB98-2
ANKRD12	ENST00000359158.7 linkuse as main transcript	c.*673A>G		3_prime_UTR_variant, NMD_transcript_variant	4/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.49e-7

AC:

AN:

1334962

Hom.:

Cov.:

AF XY:

0.00000153

AC XY:

AN XY:

654002

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:

0.0000160

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

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

May 31, 2023

The c.1559A>G (p.N520S) alteration is located in exon 9 (coding exon 8) of the ANKRD12 gene. This alteration results from a A to G substitution at nucleotide position 1559, causing the asparagine (N) at amino acid position 520 to be replaced by a serine (S). 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

0.060

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

1.7

DANN

Benign

0.82

DEOGEN2

Benign

0.0072

T;.

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.44

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.035

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.20

N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

0.28

N;.

REVEL

Benign

0.21

Sift

Benign

0.38

T;.

Sift4G

Benign

0.98

T;T

Polyphen

0.0

B;B

Vest4

0.045

MutPred

0.12

Gain of phosphorylation at N520 (P = 0.0046);.;

MVP

0.47

ClinPred

0.13

GERP RS

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.011

gMVP

0.012

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