Variant 19-1819059-G-A 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.2723C>T(p.Ser908Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000693 in 1,602,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

REXO1
NM_020695.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.17

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=0.14461166).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REXO1	NM_020695.4 linkuse as main transcript	c.2723C>T	p.Ser908Leu	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.2723C>T	p.Ser908Leu	missense_variant	8/16	1	NM_020695.4	P2
REXO1	ENST00000643515.1 linkuse as main transcript	c.650C>T	p.Ser217Leu	missense_variant	4/12			A2
REXO1	ENST00000590936.5 linkuse as main transcript	c.104C>T	p.Ser35Leu	missense_variant, NMD_transcript_variant	2/10	5
REXO1	ENST00000586343.2 linkuse as main transcript	c.*308C>T		3_prime_UTR_variant, NMD_transcript_variant	4/6	5

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000578

AC:

AN:

242400

Hom.:

AF XY:

0.0000761

AC XY:

AN XY:

131412

show subpopulations

Gnomad AFR exome

AF:

0.000626

Gnomad AMR exome

AF:

0.0000299

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000553

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000600

AC:

AN:

1450124

Hom.:

Cov.:

AF XY:

0.0000583

AC XY:

AN XY:

720226

show subpopulations

Gnomad4 AFR exome

AF:

0.000844

Gnomad4 AMR exome

AF:

0.0000689

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000434

Gnomad4 OTH exome

AF:

0.000100

GnomAD4 genome

AF:

0.000158

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.000483

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000175

Hom.:

Bravo

AF:

0.000227

ExAC

AF:

0.0000577

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

Sep 14, 2022

The c.2723C>T (p.S908L) alteration is located in exon 8 (coding exon 8) of the REXO1 gene. This alteration results from a C to T substitution at nucleotide position 2723, causing the serine (S) at amino acid position 908 to be replaced by a leucine (L). 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

Benign

-0.40

BayesDel_noAF

Benign

-0.43

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.19

T;.

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.95

D;D

M_CAP

Uncertain

0.087

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.9

M;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.8

D;.

REVEL

Benign

0.16

Sift

Uncertain

0.0090

D;.

Sift4G

Uncertain

0.0060

D;.

Polyphen

0.62

P;.

Vest4

0.28

MVP

0.18

MPC

0.42

ClinPred

0.38

GERP RS

4.0

Varity_R

0.26

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