Genetic Variant NM_004306.4:c.814G>A (chr8-123684627-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004306.4(ANXA13):c.814G>A(p.Val272Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 1,612,152 control chromosomes in the GnomAD database, including 299,530 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.68 ( 36135 hom., cov: 31)

Exomes 𝑓: 0.60 ( 263395 hom. )

Consequence

ANXA13
NM_004306.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.738

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.775247E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA13	NM_004306.4 link	c.814G>A	p.Val272Ile	missense_variant	Exon 10 of 11	ENST00000419625.6	NP_004297.2	P27216-1Q53FB5
ANXA13	NM_001003954.3 link	c.937G>A	p.Val313Ile	missense_variant	Exon 11 of 12		NP_001003954.1	P27216-2Q53FB5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA13	ENST00000419625.6 link	c.814G>A	p.Val272Ile	missense_variant	Exon 10 of 11	1	NM_004306.4	ENSP00000390809.1		P27216-1
ANXA13	ENST00000262219.10 link	c.937G>A	p.Val313Ile	missense_variant	Exon 11 of 12	1		ENSP00000262219.6		P27216-2

Frequencies

GnomAD3 genomes

AF:

0.676

AC:

102784

AN:

151978

Hom.:

36080

Cov.:

show subpopulations

Gnomad AFR

AF:

0.881

Gnomad AMI

AF:

0.665

Gnomad AMR

AF:

0.646

Gnomad ASJ

AF:

0.539

Gnomad EAS

AF:

0.498

Gnomad SAS

AF:

0.708

Gnomad FIN

AF:

0.628

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.586

Gnomad OTH

AF:

0.635

GnomAD3 exomes

AF:

0.617

AC:

155127

AN:

251374

Hom.:

48845

AF XY:

0.616

AC XY:

83646

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.886

Gnomad AMR exome

AF:

0.610

Gnomad ASJ exome

AF:

0.536

Gnomad EAS exome

AF:

0.498

Gnomad SAS exome

AF:

0.697

Gnomad FIN exome

AF:

0.624

Gnomad NFE exome

AF:

0.584

Gnomad OTH exome

AF:

0.623

GnomAD4 exome

AF:

0.597

AC:

871455

AN:

1460056

Hom.:

263395

Cov.:

AF XY:

0.600

AC XY:

435526

AN XY:

726476

show subpopulations

Gnomad4 AFR exome

AF:

0.891

Gnomad4 AMR exome

AF:

0.619

Gnomad4 ASJ exome

AF:

0.538

Gnomad4 EAS exome

AF:

0.473

Gnomad4 SAS exome

AF:

0.697

Gnomad4 FIN exome

AF:

0.627

Gnomad4 NFE exome

AF:

0.583

Gnomad4 OTH exome

AF:

0.613

GnomAD4 genome

AF:

0.677

AC:

102898

AN:

152096

Hom.:

36135

Cov.:

AF XY:

0.676

AC XY:

50260

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.881

Gnomad4 AMR

AF:

0.645

Gnomad4 ASJ

AF:

0.539

Gnomad4 EAS

AF:

0.498

Gnomad4 SAS

AF:

0.708

Gnomad4 FIN

AF:

0.628

Gnomad4 NFE

AF:

0.586

Gnomad4 OTH

AF:

0.637

Alfa

AF:

0.600

Hom.:

69751

Bravo

AF:

0.681

TwinsUK

AF:

0.584

AC:

2164

ALSPAC

AF:

0.598

AC:

2306

ESP6500AA

AF:

0.872

AC:

3843

ESP6500EA

AF:

0.585

AC:

5029

ExAC

AF:

0.624

AC:

75745

Asia WGS

AF:

0.632

AC:

2200

AN:

3478

EpiCase

AF:

0.583

EpiControl

AF:

0.584

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.0

DANN

Benign

0.51

DEOGEN2

Benign

0.0043

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.55

T;T

MetaRNN

Benign

0.0000088

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.97

.;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.13

N;N

REVEL

Benign

0.018

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.024

MPC

0.11

ClinPred

0.0042

GERP RS

0.12

Varity_R

0.022

gMVP

0.18

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over