Variant 4-78582249-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005139.3(ANXA3):c.271C>G(p.Pro91Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,461,310 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ANXA3
NM_005139.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.37

Variant links:

Genes affected

ANXA3 (HGNC:541): (annexin A3) 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. This protein functions in the inhibition of phopholipase A2 and cleavage of inositol 1,2-cyclic phosphate to form inositol 1-phosphate. This protein may also play a role in anti-coagulation. [provided by RefSeq, Jul 2008]

ANXA3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANXA3	NM_005139.3 linkuse as main transcript	c.271C>G	p.Pro91Ala	missense_variant	5/13	ENST00000264908.11
ANXA3	XM_047450154.1 linkuse as main transcript	c.271C>G	p.Pro91Ala	missense_variant	5/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANXA3	ENST00000264908.11 linkuse as main transcript	c.271C>G	p.Pro91Ala	missense_variant	5/13	1	NM_005139.3	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250912

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135578

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461310

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726934

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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 23, 2021

The c.271C>G (p.P91A) alteration is located in exon 5 (coding exon 4) of the ANXA3 gene. This alteration results from a C to G substitution at nucleotide position 271, causing the proline (P) at amino acid position 91 to be replaced by an alanine (A). 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

0.10

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Benign

-0.20

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.19

T;T;T;.;T;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.87

D;.;D;D;D;D

M_CAP

Benign

0.0070

MetaRNN

Uncertain

0.54

D;D;D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.48

PROVEAN

Pathogenic

-4.4

D;D;D;D;D;D

REVEL

Benign

0.20

Sift

Benign

0.085

T;T;T;D;D;D

Sift4G

Benign

0.077

T;T;T;D;D;T

Polyphen

0.99

D;.;.;.;.;.

Vest4

0.55

MutPred

0.48

Loss of catalytic residue at P90 (P = 0.0185);.;.;Loss of catalytic residue at P90 (P = 0.0185);Loss of catalytic residue at P90 (P = 0.0185);Loss of catalytic residue at P90 (P = 0.0185);

MVP

0.64

MPC

0.34

ClinPred

0.98

GERP RS

5.2

Varity_R

0.36

gMVP

0.51

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