Variant 10-46384828-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000619162.5(ANXA8L1):c.547G>A(p.Ala183Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000372 in 1,612,876 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 24)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

ANXA8L1
ENST00000619162.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.33

Variant links:

Genes affected

ANXA8L1 (HGNC:23334): (annexin A8 like 1) This gene encodes a member of the annexin family of evolutionarily conserved Ca2+ and phospholipid binding proteins. The encoded protein may function as an an anticoagulant that indirectly inhibits the thromboplastin-specific complex. Overexpression of this gene has been associated with acute myelocytic leukemia. A highly similar duplicated copy of this gene is found in close proximity on the long arm of chromosome 10. [provided by RefSeq, Apr 2014]

ANXA8L1 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	Protein
ANXA8L1	NM_001098845.3 linkuse as main transcript	c.547G>A	p.Ala183Thr	missense_variant	7/12	ENST00000619162.5	NP_001092315.2
ANXA8L1	NM_001278924.2 linkuse as main transcript	c.490G>A	p.Ala164Thr	missense_variant	5/9		NP_001265853.1
ANXA8L1	NM_001278923.2 linkuse as main transcript	c.376G>A	p.Ala126Thr	missense_variant	5/10		NP_001265852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA8L1	ENST00000619162.5 linkuse as main transcript	c.547G>A	p.Ala183Thr	missense_variant	7/12	1	NM_001098845.3	ENSP00000480221	P1	Q5VT79-1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151378

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000490

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:

0.0000558

AC:

AN:

251020

Hom.:

AF XY:

0.0000516

AC XY:

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000390

AC:

AN:

1461498

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

727056

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151378

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73910

show subpopulations

Gnomad4 AFR

AF:

0.0000490

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

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Jan 27, 2022

The c.547G>A (p.A183T) alteration is located in exon 7 (coding exon 7) of the ANXA8L2 gene. This alteration results from a G to A substitution at nucleotide position 547, causing the alanine (A) at amino acid position 183 to be replaced by a threonine (T). 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

Pathogenic

0.79

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.34

T;.;.;T;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.96

D;D;D;D;D

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.73

D;D;D;D;D

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;N;N;N

Sift4G

Uncertain

0.011

D;D;D;D;D

Polyphen

1.0

.;.;D;D;D

Vest4

0.62

MVP

0.26

ClinPred

0.95

GERP RS

1.8

Varity_R

0.17

gMVP

0.45

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