Variant 2-96839562-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_144994.8(ANKRD23):c.905G>A(p.Arg302His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000543 in 1,460,072 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00056 ( 2 hom. )

Consequence

ANKRD23
NM_144994.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.450

Variant links:

Genes affected

ANKRD23 (HGNC:24470): (ankyrin repeat domain 23) This gene is a member of the muscle ankyrin repeat protein (MARP) family and encodes a protein with four tandem ankyrin-like repeats. The protein is localized to the nucleus, functioning as a transcriptional regulator. Expression of this protein is induced during recovery following starvation. [provided by RefSeq, Jul 2008]

ANKRD23 links:

ANKRD39 (HGNC:28640): (ankyrin repeat domain 39) Predicted to contribute to ubiquitin-protein transferase activity. Predicted to be involved in protein K6-linked ubiquitination. Predicted to be part of BRCA1-A complex and BRCA1-BARD1 complex. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD39 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0109246075).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD23	NM_144994.8 link	c.905G>A	p.Arg302His	missense_variant	9/9	ENST00000318357.9	NP_659431.5	Q86SG2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD23	ENST00000318357.9 link	c.905G>A	p.Arg302His	missense_variant	9/9	1	NM_144994.8	ENSP00000321679.4		Q86SG2-1

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000706

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000463

AC:

AN:

92952

Hom.:

AF XY:

0.000539

AC XY:

AN XY:

50050

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.000144

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000905

Gnomad OTH exome

AF:

0.000406

GnomAD4 exome

AF:

0.000561

AC:

734

AN:

1307820

Hom.:

Cov.:

AF XY:

0.000536

AC XY:

341

AN XY:

635824

show subpopulations

Gnomad4 AFR exome

AF:

0.000208

Gnomad4 AMR exome

AF:

0.000130

Gnomad4 ASJ exome

AF:

0.0000526

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000838

Gnomad4 NFE exome

AF:

0.000666

Gnomad4 OTH exome

AF:

0.000500

GnomAD4 genome

AF:

0.000388

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000721

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000249

Hom.:

Bravo

AF:

0.000438

ESP6500AA

AF:

0.000490

AC:

ESP6500EA

AF:

0.000618

AC:

ExAC

AF:

0.000405

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Apr 06, 2024

The c.905G>A (p.R302H) alteration is located in exon 9 (coding exon 9) of the ANKRD23 gene. This alteration results from a G to A substitution at nucleotide position 905, causing the arginine (R) at amino acid position 302 to be replaced by a histidine (H). 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

0.13

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.020

T;T;.

Eigen

Benign

-0.068

Eigen_PC

Benign

-0.033

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.78

.;T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-0.36

MutationAssessor

Benign

1.8

L;L;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.12

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.058

T;T;T

Polyphen

1.0

D;D;B

Vest4

0.22

MVP

0.54

MPC

0.22

ClinPred

0.030

GERP RS

4.4

Varity_R

0.10

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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