Variant 17-29593658-G-C 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_152345.5(ANKRD13B):c.37G>C(p.Glu13Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,424,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

ANKRD13B
NM_152345.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.06

Variant links:

Genes affected

ANKRD13B (HGNC:26363): (ankyrin repeat domain 13B) Enables ubiquitin-dependent protein binding activity. Involved in negative regulation of receptor internalization. Located in endosome; perinuclear region of cytoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD13B links:

ANKRD13B (HGNC:):

ANKRD13B links:

GIT1 (HGNC:4272): (GIT ArfGAP 1) Enables gamma-tubulin binding activity. Involved in positive regulation of microtubule nucleation and regulation of cytokinesis. Located in several cellular components, including focal adhesion; microtubule cytoskeleton; and mitochondrion. Implicated in attention deficit hyperactivity disorder. Biomarker of Huntington's disease. [provided by Alliance of Genome Resources, Apr 2022]

GIT1 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=0.065149605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD13B	NM_152345.5 linkuse as main transcript	c.37G>C	p.Glu13Gln	missense_variant	1/15	ENST00000394859.8	NP_689558.4	Q86YJ7-1A0A024QZ29B3KS27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD13B	ENST00000394859.8 linkuse as main transcript	c.37G>C	p.Glu13Gln	missense_variant	1/15	2	NM_152345.5	ENSP00000378328.3		Q86YJ7-1

Frequencies

GnomAD3 genomes

AF:

0.000173

AC:

AN:

150586

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000997

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000296

Gnomad OTH

AF:

0.000963

GnomAD3 exomes

AF:

0.000261

AC:

AN:

88274

Hom.:

AF XY:

0.000282

AC XY:

AN XY:

49646

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00120

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000483

Gnomad NFE exome

AF:

0.000267

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000143

AC:

182

AN:

1273762

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

111

AN XY:

627756

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00140

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000306

Gnomad4 FIN exome

AF:

0.000449

Gnomad4 NFE exome

AF:

0.000122

Gnomad4 OTH exome

AF:

0.000138

GnomAD4 genome

AF:

0.000173

AC:

AN:

150586

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

AN XY:

73504

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000997

Gnomad4 NFE

AF:

0.000296

Gnomad4 OTH

AF:

0.000963

Alfa

AF:

0.000176

Hom.:

Bravo

AF:

0.000125

ExAC

AF:

0.000105

AC:

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

Oct 26, 2022

The c.37G>C (p.E13Q) alteration is located in exon 1 (coding exon 1) of the ANKRD13B gene. This alteration results from a G to C substitution at nucleotide position 37, causing the glutamic acid (E) at amino acid position 13 to be replaced by a glutamine (Q). 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

0.23

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Benign

0.58

DEOGEN2

Benign

0.020

T;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.69

T;.

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.065

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.55

N;N

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

0.25

.;N

REVEL

Benign

0.12

Sift

Benign

0.59

.;T

Sift4G

Benign

0.56

T;T

Polyphen

0.017

B;B

Vest4

0.16

MutPred

0.29

Gain of MoRF binding (P = 0.0241);Gain of MoRF binding (P = 0.0241);

MVP

0.42

MPC

0.93

ClinPred

0.0060

GERP RS

3.3

Varity_R

0.064

gMVP

0.42

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