19-1819113-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_020695.4(REXO1):c.2669T>C(p.Val890Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,578,436 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 7 hom., cov: 34)

Exomes 𝑓: 0.0011 ( 28 hom. )

Consequence

REXO1
NM_020695.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.42

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020196736).

BP6

Variant 19-1819113-A-G is Benign according to our data. Variant chr19-1819113-A-G is described in ClinVar as [Benign]. Clinvar id is 773896.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00156 (238/152160) while in subpopulation EAS AF= 0.04 (206/5148). AF 95% confidence interval is 0.0355. There are 7 homozygotes in gnomad4. There are 125 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REXO1	NM_020695.4 linkuse as main transcript	c.2669T>C	p.Val890Ala	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.2669T>C	p.Val890Ala	missense_variant	8/16	1	NM_020695.4	P2
REXO1	ENST00000643515.1 linkuse as main transcript	c.596T>C	p.Val199Ala	missense_variant	4/12			A2
REXO1	ENST00000590936.5 linkuse as main transcript	c.50T>C	p.Val17Ala	missense_variant, NMD_transcript_variant	2/10	5
REXO1	ENST00000586343.2 linkuse as main transcript	c.*254T>C		3_prime_UTR_variant, NMD_transcript_variant	4/6	5

Frequencies

GnomAD3 genomes

AF:

0.00159

AC:

241

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0405

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00320

AC:

724

AN:

226298

Hom.:

AF XY:

0.00297

AC XY:

365

AN XY:

122818

show subpopulations

Gnomad AFR exome

AF:

0.0000638

Gnomad AMR exome

AF:

0.0000988

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0384

Gnomad SAS exome

AF:

0.00137

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000196

Gnomad OTH exome

AF:

0.00202

GnomAD4 exome

AF:

0.00107

AC:

1528

AN:

1426276

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

778

AN XY:

705590

show subpopulations

Gnomad4 AFR exome

AF:

0.0000309

Gnomad4 AMR exome

AF:

0.0000748

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0313

Gnomad4 SAS exome

AF:

0.00164

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000147

Gnomad4 OTH exome

AF:

0.00244

GnomAD4 genome

AF:

0.00156

AC:

238

AN:

152160

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

125

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0400

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00150

Hom.:

Bravo

AF:

0.00148

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00287

AC:

348

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.72

Cadd

Benign

Dann

Benign

0.80

DEOGEN2

Benign

0.027

T;.

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.74

T;T

MetaRNN

Benign

0.0020

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.46

N;.

MutationTaster

Benign

0.99

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.083

Sift

Benign

0.30

T;.

Sift4G

Benign

0.73

T;.

Polyphen

0.11

B;.

Vest4

0.36

MVP

0.11

MPC

0.13

ClinPred

0.011

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.060

gMVP

0.56

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