Genetic Variant ANKRD13D:p.Arg116His (chr11-67290442-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_207354.3(ANKRD13D):c.347G>A(p.Arg116His) variant causes a missense change. The variant allele was found at a frequency of 0.00000633 in 1,579,770 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: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

ANKRD13D
NM_207354.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.84

Publications

1 publications found

Variant links:

Genes affected

ANKRD13D (HGNC:27880): (ankyrin repeat domain 13D) The protein encoded by this gene is a member of the ankyrin repeat domain (ANKRD) 13 family, which currently consists of four proteins containing ubiquitin-interacting motifs. These proteins are integral membrane proteins that bind specifically to Lys-63-linked ubiquitin chains on membrane-bound proteins, targeting those proteins for rapid internalization. [provided by RefSeq, Dec 2016]

ANKRD13D links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32529545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD13D	NM_207354.3 link	c.347G>A	p.Arg116His	missense_variant	Exon 3 of 15	ENST00000511455.7	NP_997237.2	Q6ZTN6-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD13D	ENST00000511455.7 link	c.347G>A	p.Arg116His	missense_variant	Exon 3 of 15	1	NM_207354.3	ENSP00000427130.2		Q6ZTN6-3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000102

AC:

AN:

195802

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000847

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:

0.0000118

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000490

AC:

AN:

1427564

Hom.:

Cov.:

AF XY:

0.00000566

AC XY:

AN XY:

706610

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33036

American (AMR)

AF:

0.00

AC:

AN:

39066

Ashkenazi Jewish (ASJ)

AF:

0.0000393

AC:

AN:

25438

East Asian (EAS)

AF:

0.00

AC:

AN:

38532

South Asian (SAS)

AF:

0.00

AC:

AN:

81580

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50748

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4144

European-Non Finnish (NFE)

AF:

0.00000547

AC:

AN:

1095988

Other (OTH)

AF:

0.00

AC:

AN:

59032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000264

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 25, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.347G>A (p.R116H) alteration is located in exon 3 (coding exon 3) of the ANKRD13D gene. This alteration results from a G to A substitution at nucleotide position 347, causing the arginine (R) at amino acid position 116 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

0.079

BayesDel_addAF

Uncertain

0.036

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;.;T;T;.

Eigen

Benign

-0.0045

Eigen_PC

Benign

0.068

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.95

.;D;.;D;D

M_CAP

Benign

0.0061

MetaRNN

Benign

0.33

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.;L;L;.

PhyloP100

5.8

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.4

D;D;D;D;.

REVEL

Benign

0.15

Sift

Benign

0.094

T;T;T;T;.

Sift4G

Benign

0.073

T;T;T;T;T

Polyphen

0.23

B;B;B;B;.

Vest4

0.73

MutPred

0.34

Loss of MoRF binding (P = 0.1512);.;Loss of MoRF binding (P = 0.1512);Loss of MoRF binding (P = 0.1512);Loss of MoRF binding (P = 0.1512);

MVP

0.49

MPC

1.3

ClinPred

0.80

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.17

gMVP

0.58

Mutation Taster

=82/18

polymorphism

(source)

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

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chr11-67290442-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over