Variant 8-123688898-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004306.4(ANXA13):c.691G>A(p.Asp231Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000341 in 1,613,882 control chromosomes in the GnomAD database, including 2 homozygotes. 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 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 2 hom. )

Consequence

ANXA13
NM_004306.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.79

Variant links:

Genes affected

ANXA13 (HGNC:536): (annexin A13) This gene encodes a member of the annexin family. Members of this calcium-dependent phospholipid-binding protein family play a role in the regulation of cellular growth and in signal transduction pathways. The specific function of this gene has not yet been determined; however, it is associated with the plasma membrane of undifferentiated, proliferating endothelial cells and differentiated villus enterocytes. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ANXA13 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07942939).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANXA13	NM_004306.4 linkuse as main transcript	c.691G>A	p.Asp231Asn	missense_variant	9/11	ENST00000419625.6	NP_004297.2	P27216-1Q53FB5
ANXA13	NM_001003954.3 linkuse as main transcript	c.814G>A	p.Asp272Asn	missense_variant	10/12		NP_001003954.1	P27216-2Q53FB5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA13	ENST00000419625.6 linkuse as main transcript	c.691G>A	p.Asp231Asn	missense_variant	9/11	1	NM_004306.4	ENSP00000390809.1		P27216-1
ANXA13	ENST00000262219.10 linkuse as main transcript	c.814G>A	p.Asp272Asn	missense_variant	10/12	1		ENSP00000262219.6		P27216-2

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000453

AC:

114

AN:

251456

Hom.:

AF XY:

0.000500

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000549

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000555

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000563

Gnomad OTH exome

AF:

0.00195

GnomAD4 exome

AF:

0.000343

AC:

501

AN:

1461650

Hom.:

Cov.:

AF XY:

0.000369

AC XY:

268

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000604

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.000429

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000335

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.000322

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000471

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000540

Hom.:

Bravo

AF:

0.000412

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000428

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.000771

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 22, 2021

The c.814G>A (p.D272N) alteration is located in exon 10 (coding exon 10) of the ANXA13 gene. This alteration results from a G to A substitution at nucleotide position 814, causing the aspartic acid (D) at amino acid position 272 to be replaced by an asparagine (N). 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

0.19

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.051

.;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.0083

MetaRNN

Benign

0.079

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.3

.;L

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.3

D;D

REVEL

Benign

0.087

Sift

Benign

0.16

T;T

Sift4G

Benign

0.28

T;T

Polyphen

0.54

P;P

Vest4

0.35

MVP

0.45

MPC

0.14

ClinPred

0.039

GERP RS

3.9

Varity_R

0.22

gMVP

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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