Genetic Variant ANXA8L1:p.Thr207Met (chr10-46385447-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001098845.3(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. 10/17 in silico tools predict 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
NM_001098845.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.248

Publications

2 publications found

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:

ENSG00000285402 (HGNC:):

ENSG00000285402 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

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

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098845.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANXA8L1	NM_001098845.3	MANE Select	c.620C>T	p.Thr207Met	missense	Exon 8 of 12	NP_001092315.2	Q5VT79-1
ANXA8L1	NM_001278924.2		c.563C>T	p.Thr188Met	missense	Exon 6 of 9	NP_001265853.1	Q5VT79-2
ANXA8L1	NM_001278923.2		c.449C>T	p.Thr150Met	missense	Exon 6 of 10	NP_001265852.1	B4DTF2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANXA8L1	ENST00000619162.5	TSL:1 MANE Select	c.620C>T	p.Thr207Met	missense	Exon 8 of 12	ENSP00000480221.1	Q5VT79-1
ANXA8L1	ENST00000622769.4	TSL:1	c.563C>T	p.Thr188Met	missense	Exon 6 of 9	ENSP00000483608.1	Q5VT79-2
ANXA8L1	ENST00000584982.7	TSL:2	c.734C>T	p.Thr245Met	missense	Exon 8 of 12	ENSP00000462716.2	A0A075B752

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

GnomAD2 exomes

AF:

0.00193

AC:

249

AN:

128908

AF XY:

0.00208

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 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

African (AFR)

AF:

0.000239

AC:

AN:

20922

American (AMR)

AF:

0.000259

AC:

AN:

34734

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21016

East Asian (EAS)

AF:

0.00

AC:

AN:

39364

South Asian (SAS)

AF:

0.0000959

AC:

AN:

72986

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40990

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3294

European-Non Finnish (NFE)

AF:

0.0000217

AC:

AN:

784722

Other (OTH)

AF:

0.0000869

AC:

AN:

46022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000110

AC:

AN:

100116

Hom.:

Cov.:

AF XY:

0.000186

AC XY:

AN XY:

48418

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

22254

American (AMR)

AF:

0.000714

AC:

AN:

9804

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2568

East Asian (EAS)

AF:

0.00

AC:

AN:

5010

South Asian (SAS)

AF:

0.00

AC:

AN:

3428

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6652

Middle Eastern (MID)

AF:

0.00

AC:

AN:

232

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

48186

Other (OTH)

AF:

0.00

AC:

AN:

1370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000843

Hom.:

ESP6500AA

AF:

0.000530

AC:

ESP6500EA

AF:

0.00127

AC:

ExAC

AF:

0.00184

AC:

159

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Benign

0.15

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.045

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.015

MetaRNN

Benign

0.023

MetaSVM

Benign

-1.1

PhyloP100

0.25

Sift4G

Uncertain

0.030

Polyphen

1.0

Vest4

0.36

MVP

0.29

ClinPred

0.059

GERP RS

1.8

Varity_R

0.10

gMVP

0.33

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over