Variant 6-31970635-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005510.4(DXO):c.783C>A(p.His261Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0871 in 1,613,134 control chromosomes in the GnomAD database, including 7,112 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.10 ( 858 hom., cov: 32)

Exomes 𝑓: 0.086 ( 6254 hom. )

Consequence

DXO
NM_005510.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.62

Variant links:

Genes affected

DXO (HGNC:2992): (decapping exoribonuclease) This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. The function of its protein product is unknown, but its ubiquitous expression and conservation in both simple and complex eukaryotes suggests that this may be a housekeeping gene. [provided by RefSeq, Jul 2008]

DXO links:

DXO (HGNC:):

DXO 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=0.0015405118).

BP6

Variant 6-31970635-G-T is Benign according to our data. Variant chr6-31970635-G-T is described in ClinVar as [Benign]. Clinvar id is 403444.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DXO	NM_005510.4 linkuse as main transcript	c.783C>A	p.His261Gln	missense_variant	4/7	ENST00000337523.10	NP_005501.2	O77932A0A024RCW8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DXO	ENST00000337523.10 linkuse as main transcript	c.783C>A	p.His261Gln	missense_variant	4/7	1	NM_005510.4	ENSP00000337759.5		O77932

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15343

AN:

152086

Hom.:

863

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.0803

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.0364

Gnomad SAS

AF:

0.152

Gnomad FIN

AF:

0.0539

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0862

Gnomad OTH

AF:

0.121

GnomAD3 exomes

AF:

0.0897

AC:

22224

AN:

247692

Hom.:

1267

AF XY:

0.0916

AC XY:

12328

AN XY:

134552

show subpopulations

Gnomad AFR exome

AF:

0.148

Gnomad AMR exome

AF:

0.0750

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.0339

Gnomad SAS exome

AF:

0.129

Gnomad FIN exome

AF:

0.0537

Gnomad NFE exome

AF:

0.0828

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.0857

AC:

125159

AN:

1460930

Hom.:

6254

Cov.:

AF XY:

0.0868

AC XY:

63078

AN XY:

726774

show subpopulations

Gnomad4 AFR exome

AF:

0.151

Gnomad4 AMR exome

AF:

0.0783

Gnomad4 ASJ exome

AF:

0.178

Gnomad4 EAS exome

AF:

0.0213

Gnomad4 SAS exome

AF:

0.131

Gnomad4 FIN exome

AF:

0.0538

Gnomad4 NFE exome

AF:

0.0814

Gnomad4 OTH exome

AF:

0.0978

GnomAD4 genome

AF:

0.101

AC:

15346

AN:

152204

Hom.:

858

Cov.:

AF XY:

0.0993

AC XY:

7389

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.138

Gnomad4 AMR

AF:

0.0802

Gnomad4 ASJ

AF:

0.173

Gnomad4 EAS

AF:

0.0367

Gnomad4 SAS

AF:

0.151

Gnomad4 FIN

AF:

0.0539

Gnomad4 NFE

AF:

0.0862

Gnomad4 OTH

AF:

0.120

Alfa

AF:

0.0936

Hom.:

1135

Bravo

AF:

0.107

TwinsUK

AF:

0.0709

AC:

263

ALSPAC

AF:

0.0763

AC:

294

ESP6500AA

AF:

0.147

AC:

444

ESP6500EA

AF:

0.0915

AC:

496

ExAC

AF:

0.0897

AC:

10854

Asia WGS

AF:

0.0740

AC:

258

AN:

3478

EpiCase

AF:

0.0981

EpiControl

AF:

0.0944

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.00060

T;T;T

Eigen

Benign

0.036

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.82

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.54

N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.22

N;N;N

REVEL

Benign

0.040

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.12

B;B;B

Vest4

0.16

MutPred

0.14

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MPC

0.41

ClinPred

0.0047

GERP RS

3.6

Varity_R

0.26

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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