Variant 8-123702700-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000419625.6(ANXA13):c.128G>T(p.Gly43Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ANXA13
ENST00000419625.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.852

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16705972).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANXA13	NM_004306.4 linkuse as main transcript	c.128G>T	p.Gly43Val	missense_variant	3/11	ENST00000419625.6	NP_004297.2	P27216-1Q53FB5
ANXA13	NM_001003954.3 linkuse as main transcript	c.251G>T	p.Gly84Val	missense_variant	4/12		NP_001003954.1	P27216-2Q53FB5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ANXA13	ENST00000419625.6 linkuse as main transcript	c.128G>T	p.Gly43Val	missense_variant	3/11	1	NM_004306.4	ENSP00000390809.1	P27216-1
ANXA13	ENST00000262219.10 linkuse as main transcript	c.251G>T	p.Gly84Val	missense_variant	4/12	1		ENSP00000262219.6	P27216-2
ANXA13	ENST00000520519.1 linkuse as main transcript	c.41G>T	p.Gly14Val	missense_variant	3/6	4		ENSP00000429358.1	E5RIN3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251448

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Aug 02, 2022

The c.251G>T (p.G84V) alteration is located in exon 4 (coding exon 4) of the ANXA13 gene. This alteration results from a G to T substitution at nucleotide position 251, causing the glycine (G) at amino acid position 84 to be replaced by a valine (V). 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

0.17

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.021

.;T;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.69

T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.97

.;L;.

MutationTaster

Benign

0.87

D;D

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.028

Sift

Benign

0.14

T;T;D

Sift4G

Benign

0.10

T;T;T

Polyphen

0.043

B;B;.

Vest4

0.27

MutPred

0.30

.;Loss of disorder (P = 0.0318);.;

MVP

0.44

MPC

0.18

ClinPred

0.090

GERP RS

2.5

Varity_R

0.14

gMVP

0.31

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

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