Variant chr11-114439657-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000265881.10(REXO2):c.129G>A(p.Met43Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000283 in 1,570,834 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 2 hom. )

Consequence

REXO2
ENST00000265881.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.64

Variant links:

Genes affected

REXO2 (HGNC:17851): (RNA exonuclease 2) This gene encodes a 3'-to-5' exonuclease specific for small (primarily 5 nucleotides or less in length) single-stranded RNA and DNA oligomers. This protein may have a role in DNA repair, replication, and recombination, and in RNA processing and degradation. It may also be involved in resistance of human cells to UV-C-induced cell death through its role in the DNA repair process. [provided by RefSeq, Nov 2011]

REXO2 links:

ENSG00000255663 (HGNC:):

ENSG00000255663 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11876109).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REXO2	NM_015523.4 linkuse as main transcript	c.129G>A	p.Met43Ile	missense_variant	1/7	ENST00000265881.10	NP_056338.2	Q9Y3B8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REXO2	ENST00000265881.10 linkuse as main transcript	c.129G>A	p.Met43Ile	missense_variant	1/7	1	NM_015523.4	ENSP00000265881.5		Q9Y3B8-1
ENSG00000255663	ENST00000544347.1 linkuse as main transcript	n.*123-999G>A		intron_variant		3		ENSP00000461728.1		I3L521

Frequencies

GnomAD3 genomes

AF:

0.000368

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000294

AC:

AN:

187356

Hom.:

AF XY:

0.000344

AC XY:

AN XY:

101776

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000719

Gnomad NFE exome

AF:

0.000487

Gnomad OTH exome

AF:

0.000849

GnomAD4 exome

AF:

0.000274

AC:

389

AN:

1418630

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

209

AN XY:

702938

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00105

Gnomad4 NFE exome

AF:

0.000293

Gnomad4 OTH exome

AF:

0.000307

GnomAD4 genome

AF:

0.000368

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.000720

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000822

Hom.:

Bravo

AF:

0.000178

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000332

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

Mar 02, 2023

The c.129G>A (p.M43I) alteration is located in exon 1 (coding exon 1) of the REXO2 gene. This alteration results from a G to A substitution at nucleotide position 129, causing the methionine (M) at amino acid position 43 to be replaced by an isoleucine (I). 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

Uncertain

0.46

BayesDel_addAF

Uncertain

0.071

BayesDel_noAF

Pathogenic

0.32

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;T;.;T;T

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

D;.;D;D;D

M_CAP

Uncertain

0.087

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Uncertain

0.37

MutationAssessor

Benign

-0.24

N;N;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.50

.;N;N;N;N

REVEL

Uncertain

0.58

Sift

Benign

0.25

.;T;T;T;T

Sift4G

Benign

0.27

T;T;T;T;T

Polyphen

0.17

B;B;.;.;P

Vest4

0.63

MutPred

0.63

Loss of disorder (P = 0.0589);Loss of disorder (P = 0.0589);Loss of disorder (P = 0.0589);Loss of disorder (P = 0.0589);Loss of disorder (P = 0.0589);

MVP

0.77

MPC

0.46

ClinPred

0.10

GERP RS

5.3

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Varity_R

0.66

gMVP

0.60

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