Variant 4-168139570-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000359299.8(ANXA10):c.185T>C(p.Met62Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000849 in 1,609,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00088 ( 0 hom. )

Consequence

ANXA10
ENST00000359299.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.81

Variant links:

Genes affected

ANXA10 (HGNC:534): (annexin A10) This gene encodes a member of the annexin family. Members of this calcium-dependent phospholipid-binding protein family play a role in the regulation of cellular growth and in signal transduction pathways. The function of this gene has not yet been determined. [provided by RefSeq, Jul 2008]

ANXA10 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=0.07150185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANXA10	NM_007193.5 linkuse as main transcript	c.185T>C	p.Met62Thr	missense_variant	3/12	ENST00000359299.8	NP_009124.2
ANXA10	XM_011531571.3 linkuse as main transcript	c.185T>C	p.Met62Thr	missense_variant	3/13		XP_011529873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA10	ENST00000359299.8 linkuse as main transcript	c.185T>C	p.Met62Thr	missense_variant	3/12	1	NM_007193.5	ENSP00000352248	P1

Frequencies

GnomAD3 genomes

AF:

0.000591

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00100

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000514

AC:

129

AN:

250756

Hom.:

AF XY:

0.000443

AC XY:

AN XY:

135518

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000666

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.000803

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000875

AC:

1276

AN:

1457594

Hom.:

Cov.:

AF XY:

0.000800

AC XY:

580

AN XY:

724582

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.000192

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.00108

Gnomad4 OTH exome

AF:

0.000615

GnomAD4 genome

AF:

0.000591

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.000471

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00100

Gnomad4 OTH

AF:

0.00144

Alfa

AF:

0.00101

Hom.:

Bravo

AF:

0.000763

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.000511

AC:

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

Aug 04, 2021

The c.185T>C (p.M62T) alteration is located in exon 3 (coding exon 3) of the ANXA10 gene. This alteration results from a T to C substitution at nucleotide position 185, causing the methionine (M) at amino acid position 62 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

Benign

0.16

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.47

DEOGEN2

Benign

0.0056

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.58

M_CAP

Benign

0.0072

MetaRNN

Benign

0.072

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.29

REVEL

Benign

0.11

Sift

Benign

0.56

Sift4G

Benign

0.59

Polyphen

0.0

Vest4

0.49

MVP

0.088

MPC

0.051

ClinPred

0.0070

GERP RS

3.3

Varity_R

0.20

gMVP

0.38

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