5-151117141-G-A

Variant names:

Variant summary

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

The NM_001155.5(ANXA6):c.1558C>T(p.Arg520Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 1,591,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

ANXA6
NM_001155.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.16

Variant links:

Genes affected

ANXA6 (HGNC:544): (annexin A6) Annexin VI belongs to a family of calcium-dependent membrane and phospholipid binding proteins. Several members of the annexin family have been implicated in membrane-related events along exocytotic and endocytotic pathways. The annexin VI gene is approximately 60 kbp long and contains 26 exons. It encodes a protein of about 68 kDa that consists of eight 68-amino acid repeats separated by linking sequences of variable lengths. It is highly similar to human annexins I and II sequences, each of which contain four such repeats. Annexin VI has been implicated in mediating the endosome aggregation and vesicle fusion in secreting epithelia during exocytosis. Alternatively spliced transcript variants have been described. [provided by RefSeq, Aug 2010]

ANXA6 links:

Genome browser will be placed here

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=0.19697398).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA6	NM_001155.5 link	c.1558C>T	p.Arg520Trp	missense_variant	Exon 20 of 26	ENST00000354546.10	NP_001146.2	P08133-1A0A0S2Z2Z6
ANXA6	NM_001363114.2 link	c.1558C>T	p.Arg520Trp	missense_variant	Exon 20 of 25		NP_001350043.1
ANXA6	NM_001193544.2 link	c.1462C>T	p.Arg488Trp	missense_variant	Exon 19 of 25		NP_001180473.1	P08133-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA6	ENST00000354546.10 link	c.1558C>T	p.Arg520Trp	missense_variant	Exon 20 of 26	1	NM_001155.5	ENSP00000346550.5		P08133-1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000604

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000600

AC:

AN:

233318

Hom.:

AF XY:

0.0000394

AC XY:

AN XY:

127060

show subpopulations

Gnomad AFR exome

AF:

0.000349

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000316

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000374

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000151

AC:

217

AN:

1439010

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

715266

show subpopulations

Gnomad4 AFR exome

AF:

0.000308

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000186

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000177

Gnomad4 OTH exome

AF:

0.0000675

GnomAD4 genome

AF:

0.000171

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.000604

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000149

Hom.:

Bravo

AF:

0.000200

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000579

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 24, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1558C>T (p.R520W) alteration is located in exon 20 (coding exon 19) of the ANXA6 gene. This alteration results from a C to T substitution at nucleotide position 1558, causing the arginine (R) at amino acid position 520 to be replaced by a tryptophan (W). 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

0.14

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

T;.;T;T

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.96

D;D;D;D

M_CAP

Benign

0.0045

MetaRNN

Benign

0.20

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.6

M;.;.;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.9

N;N;D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0080

D;D;D;D

Sift4G

Uncertain

0.015

D;D;D;D

Polyphen

0.94

P;.;.;D

Vest4

0.44

MVP

0.58

MPC

0.11

ClinPred

0.14

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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