Variant 19-1819035-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020695.4(REXO1):c.2747G>A(p.Arg916Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000726 in 1,601,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00076 ( 0 hom. )

Consequence

REXO1
NM_020695.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.15

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024344414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REXO1	NM_020695.4 linkuse as main transcript	c.2747G>A	p.Arg916Gln	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.2747G>A	p.Arg916Gln	missense_variant	8/16	1	NM_020695.4	P2
REXO1	ENST00000643515.1 linkuse as main transcript	c.674G>A	p.Arg225Gln	missense_variant	4/12			A2
REXO1	ENST00000590936.5 linkuse as main transcript	c.128G>A	p.Arg43Gln	missense_variant, NMD_transcript_variant	2/10	5
REXO1	ENST00000586343.2 linkuse as main transcript	c.*332G>A		3_prime_UTR_variant, NMD_transcript_variant	4/6	5

Frequencies

GnomAD3 genomes

AF:

0.000427

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000706

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000438

AC:

105

AN:

239574

Hom.:

AF XY:

0.000523

AC XY:

AN XY:

129994

show subpopulations

Gnomad AFR exome

AF:

0.000188

Gnomad AMR exome

AF:

0.000456

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.0000345

Gnomad FIN exome

AF:

0.0000951

Gnomad NFE exome

AF:

0.000751

Gnomad OTH exome

AF:

0.000344

GnomAD4 exome

AF:

0.000758

AC:

1098

AN:

1449140

Hom.:

Cov.:

AF XY:

0.000761

AC XY:

548

AN XY:

719738

show subpopulations

Gnomad4 AFR exome

AF:

0.0000603

Gnomad4 AMR exome

AF:

0.000508

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.000289

Gnomad4 NFE exome

AF:

0.000919

Gnomad4 OTH exome

AF:

0.000619

GnomAD4 genome

AF:

0.000427

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000706

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000685

Hom.:

Bravo

AF:

0.000510

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000454

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 09, 2021

The c.2747G>A (p.R916Q) 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 2747, causing the arginine (R) at amino acid position 916 to be replaced by a glutamine (Q). 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

0.11

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.64

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.016

T;.

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.45

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.024

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.56

N;.

MutationTaster

Benign

0.99

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.0

N;.

REVEL

Benign

0.021

Sift

Benign

0.10

T;.

Sift4G

Benign

0.81

T;.

Polyphen

0.34

B;.

Vest4

0.23

MVP

0.13

MPC

0.19

ClinPred

0.0099

GERP RS

3.2

Varity_R

0.067

gMVP

0.44

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