Genetic Variant ANXA13:p.Val272Ile (chr8-123684627-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

32 publications found

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:

ENSG00000253286 (HGNC:):

ENSG00000253286 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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
ANXA13	NM_001003954.3 link	c.937G>A	p.Val313Ile	missense_variant	Exon 11 of 12		NP_001003954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ANXA13	ENST00000419625.6 link	c.814G>A	p.Val272Ile	missense_variant	Exon 10 of 11	1	NM_004306.4	ENSP00000390809.1
ANXA13	ENST00000262219.10 link	c.937G>A	p.Val313Ile	missense_variant	Exon 11 of 12	1		ENSP00000262219.6
ENSG00000253286	ENST00000836608.1 link	n.119-28065C>T		intron_variant	Intron 1 of 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

GnomAD2 exomes

AF:

0.617

AC:

155127

AN:

251374

AF XY:

0.616

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 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

African (AFR)

AF:

0.891

AC:

29826

AN:

33466

American (AMR)

AF:

0.619

AC:

27651

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.538

AC:

14055

AN:

26130

East Asian (EAS)

AF:

0.473

AC:

18765

AN:

39690

South Asian (SAS)

AF:

0.697

AC:

60102

AN:

86222

European-Finnish (FIN)

AF:

0.627

AC:

33471

AN:

53416

Middle Eastern (MID)

AF:

0.636

AC:

3662

AN:

5762

European-Non Finnish (NFE)

AF:

0.583

AC:

646904

AN:

1110318

Other (OTH)

AF:

0.613

AC:

37019

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

16363

32726

49088

65451

81814

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17882

35764

53646

71528

89410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.677

AC:

102898

AN:

152096

Hom.:

36135

Cov.:

AF XY:

0.676

AC XY:

50260

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.881

AC:

36565

AN:

41506

American (AMR)

AF:

0.645

AC:

9854

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.539

AC:

1869

AN:

3466

East Asian (EAS)

AF:

0.498

AC:

2571

AN:

5162

South Asian (SAS)

AF:

0.708

AC:

3404

AN:

4810

European-Finnish (FIN)

AF:

0.628

AC:

6638

AN:

10572

Middle Eastern (MID)

AF:

0.643

AC:

189

AN:

294

European-Non Finnish (NFE)

AF:

0.586

AC:

39859

AN:

67992

Other (OTH)

AF:

0.637

AC:

1344

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1578

3157

4735

6314

7892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

798

1596

2394

3192

3990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.607

Hom.:

125451

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

(source)

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

PhyloP100

0.74

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

Mutation Taster

=99/1

polymorphism (auto)

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over