Variant 19-1819089-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020695.4(REXO1):c.2693G>A(p.Gly898Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000325 in 1,598,026 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

REXO1
NM_020695.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.49

Variant links:

Genes affected

REXO1 (HGNC:24616): (RNA exonuclease 1 homolog) Predicted to enable exonuclease activity. Predicted to be involved in nucleic acid phosphodiester bond hydrolysis. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

REXO1 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=0.17422163).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REXO1	NM_020695.4 linkuse as main transcript	c.2693G>A	p.Gly898Glu	missense_variant	8/16	ENST00000170168.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
REXO1	ENST00000170168.9 linkuse as main transcript	c.2693G>A	p.Gly898Glu	missense_variant	8/16	1	NM_020695.4	P2
REXO1	ENST00000643515.1 linkuse as main transcript	c.620G>A	p.Gly207Glu	missense_variant	4/12			A2
REXO1	ENST00000590936.5 linkuse as main transcript	c.74G>A	p.Gly25Glu	missense_variant, NMD_transcript_variant	2/10	5
REXO1	ENST00000586343.2 linkuse as main transcript	c.*278G>A		3_prime_UTR_variant, NMD_transcript_variant	4/6	5

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152188

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:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000548

AC:

AN:

237106

Hom.:

AF XY:

0.0000544

AC XY:

AN XY:

128678

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000309

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000348

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000103

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000304

AC:

AN:

1445720

Hom.:

Cov.:

AF XY:

0.0000334

AC XY:

AN XY:

717910

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000235

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000326

Gnomad4 OTH exome

AF:

0.0000671

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74478

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:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000412

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

May 16, 2023

The c.2693G>A (p.G898E) alteration is located in exon 8 (coding exon 8) of the REXO1 gene. This alteration results from a G to A substitution at nucleotide position 2693, causing the glycine (G) at amino acid position 898 to be replaced by a glutamic acid (E). 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

0.92

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.46

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.15

T;.

Eigen

Benign

0.17

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.063

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-4.1

D;.

REVEL

Benign

0.12

Sift

Uncertain

0.010

D;.

Sift4G

Uncertain

0.0070

D;.

Polyphen

0.97

D;.

Vest4

0.81

MutPred

0.33

Gain of solvent accessibility (P = 0.0171);.;

MVP

0.12

MPC

0.47

ClinPred

0.79

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.48

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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