Variant chr10-46385447-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000619162.5(ANXA8L1):c.620C>T(p.Thr207Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 3 hom., cov: 14)

Exomes 𝑓: 0.000039 ( 8 hom. )

Consequence

ANXA8L1
ENST00000619162.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.248

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02297765).

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ANXA8L1	NM_001098845.3 linkuse as main transcript	c.620C>T	p.Thr207Met	missense_variant	8/12	ENST00000619162.5	NP_001092315.2
ANXA8L1	NM_001278924.2 linkuse as main transcript	c.563C>T	p.Thr188Met	missense_variant	6/9		NP_001265853.1
ANXA8L1	NM_001278923.2 linkuse as main transcript	c.449C>T	p.Thr150Met	missense_variant	6/10		NP_001265852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA8L1	ENST00000619162.5 linkuse as main transcript	c.620C>T	p.Thr207Met	missense_variant	8/12	1	NM_001098845.3	ENSP00000480221	P1	Q5VT79-1

Frequencies

GnomAD3 genomes

AF:

0.000110

AC:

AN:

100116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000180

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000714

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00193

AC:

249

AN:

128908

Hom.:

AF XY:

0.00208

AC XY:

140

AN XY:

67240

show subpopulations

Gnomad AFR exome

AF:

0.000767

Gnomad AMR exome

AF:

0.00289

Gnomad ASJ exome

AF:

0.00256

Gnomad EAS exome

AF:

0.000354

Gnomad SAS exome

AF:

0.00123

Gnomad FIN exome

AF:

0.000304

Gnomad NFE exome

AF:

0.00226

Gnomad OTH exome

AF:

0.00461

GnomAD4 exome

AF:

0.0000395

AC:

AN:

1064050

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

536368

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000259

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000959

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000217

Gnomad4 OTH exome

AF:

0.0000869

GnomAD4 genome

AF:

0.000110

AC:

AN:

100116

Hom.:

Cov.:

AF XY:

0.000186

AC XY:

AN XY:

48418

show subpopulations

Gnomad4 AFR

AF:

0.000180

Gnomad4 AMR

AF:

0.000714

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ESP6500AA

AF:

0.000530

AC:

ESP6500EA

AF:

0.00127

AC:

ExAC

AF:

0.00184

AC:

159

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

Jun 18, 2021

The c.620C>T (p.T207M) alteration is located in exon 8 (coding exon 8) of the ANXA8L2 gene. This alteration results from a C to T substitution at nucleotide position 620, causing the threonine (T) at amino acid position 207 to be replaced by a methionine (M). 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

0.15

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;.;.;T;.

Eigen

Benign

0.15

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.045

LIST_S2

Pathogenic

0.97

D;D;D;D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.023

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;N;N;N

Sift4G

Uncertain

0.030

D;D;D;D;D

Polyphen

1.0, 1.0

.;.;D;D;D

Vest4

0.36

MVP

0.29

ClinPred

0.059

GERP RS

1.8

Varity_R

0.10

gMVP

0.33

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