Genetic Variant ANKRD23:p.Arg291Gln (chr2-96839595-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_144994.8(ANKRD23):c.872G>A(p.Arg291Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000375 in 1,333,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R291P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000038 ( 0 hom. )

Consequence

ANKRD23
NM_144994.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.930

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04477966).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144994.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD23	NM_144994.8	MANE Select	c.872G>A	p.Arg291Gln	missense	Exon 9 of 9	NP_659431.5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD23	ENST00000318357.9	TSL:1 MANE Select	c.872G>A	p.Arg291Gln	missense	Exon 9 of 9	ENSP00000321679.4	Q86SG2-1
ANKRD23	ENST00000962363.1		c.881G>A	p.Arg294Gln	missense	Exon 9 of 9	ENSP00000632422.1
ANKRD23	ENST00000870651.1		c.875G>A	p.Arg292Gln	missense	Exon 9 of 9	ENSP00000540710.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000834

AC:

AN:

119968

AF XY:

0.0000154

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000184

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000375

AC:

AN:

1333168

Hom.:

Cov.:

AF XY:

0.00000308

AC XY:

AN XY:

649846

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29856

American (AMR)

AF:

0.00

AC:

AN:

26880

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19592

East Asian (EAS)

AF:

0.00

AC:

AN:

36836

South Asian (SAS)

AF:

0.00

AC:

AN:

68866

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41330

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3724

European-Non Finnish (NFE)

AF:

0.00000476

AC:

AN:

1051148

Other (OTH)

AF:

0.00

AC:

AN:

54936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000873

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

2.4

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.023

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.71

M_CAP

Benign

0.027

MetaRNN

Benign

0.045

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.49

PhyloP100

-0.93

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.8

REVEL

Benign

0.12

Sift

Benign

0.19

Sift4G

Benign

0.23

Polyphen

0.0080

Vest4

0.082

MutPred

0.53

Loss of MoRF binding (P = 0.0169)

MVP

0.17

MPC

0.17

ClinPred

0.10

GERP RS

-4.0

Varity_R

0.049

gMVP

0.19

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over