Variant 5-151117834-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001155.5(ANXA6):c.1442A>G(p.Tyr481Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000652 in 1,613,268 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00048 ( 6 hom. )

Consequence

ANXA6
NM_001155.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.54

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029673308).

BP6

Variant 5-151117834-T-C is Benign according to our data. Variant chr5-151117834-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 788990.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ANXA6	NM_001155.5 linkuse as main transcript	c.1442A>G	p.Tyr481Cys	missense_variant	19/26	ENST00000354546.10	NP_001146.2
ANXA6	NM_001363114.2 linkuse as main transcript	c.1442A>G	p.Tyr481Cys	missense_variant	19/25		NP_001350043.1
ANXA6	NM_001193544.2 linkuse as main transcript	c.1346A>G	p.Tyr449Cys	missense_variant	18/25		NP_001180473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA6	ENST00000354546.10 linkuse as main transcript	c.1442A>G	p.Tyr481Cys	missense_variant	19/26	1	NM_001155.5	ENSP00000346550	P4	P08133-1

Frequencies

GnomAD3 genomes

AF:

0.00231

AC:

352

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00702

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000961

AC:

239

AN:

248712

Hom.:

AF XY:

0.000764

AC XY:

103

AN XY:

134888

show subpopulations

Gnomad AFR exome

AF:

0.00642

Gnomad AMR exome

AF:

0.000435

Gnomad ASJ exome

AF:

0.0106

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000887

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.000479

AC:

700

AN:

1460986

Hom.:

Cov.:

AF XY:

0.000461

AC XY:

335

AN XY:

726782

show subpopulations

Gnomad4 AFR exome

AF:

0.00726

Gnomad4 AMR exome

AF:

0.000604

Gnomad4 ASJ exome

AF:

0.0111

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000522

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.00231

AC:

352

AN:

152282

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

169

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00700

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00109

Hom.:

Bravo

AF:

0.00265

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00720

AC:

ESP6500EA

AF:

0.000363

AC:

ExAC

AF:

0.000976

AC:

118

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

T;.;T;T

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.94

D;D;D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.030

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.2

M;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.4

D;D;D;D

REVEL

Benign

0.28

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

1.0

D;.;.;D

Vest4

0.86

MVP

0.75

MPC

0.46

ClinPred

0.082

GERP RS

5.3

Varity_R

0.65

gMVP

0.67

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