chr6-31970635-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

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

Publications

18 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005510.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DXO	NM_005510.4	MANE Select	c.783C>A	p.His261Gln	missense	Exon 4 of 7	NP_005501.2
DXO	NM_001438478.1		c.783C>A	p.His261Gln	missense	Exon 3 of 6	NP_001425407.1
DXO	NM_001438479.1		c.783C>A	p.His261Gln	missense	Exon 4 of 7	NP_001425408.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DXO	ENST00000337523.10	TSL:1 MANE Select	c.783C>A	p.His261Gln	missense	Exon 4 of 7	ENSP00000337759.5
DXO	ENST00000375356.7	TSL:1	c.783C>A	p.His261Gln	missense	Exon 3 of 6	ENSP00000364505.3
DXO	ENST00000473976.1	TSL:1	n.1289C>A		non_coding_transcript_exon	Exon 2 of 3

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

GnomAD2 exomes

AF:

0.0897

AC:

22224

AN:

247692

AF XY:

0.0916

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 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

African (AFR)

AF:

0.151

AC:

5039

AN:

33480

American (AMR)

AF:

0.0783

AC:

3502

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

4659

AN:

26132

East Asian (EAS)

AF:

0.0213

AC:

845

AN:

39700

South Asian (SAS)

AF:

0.131

AC:

11278

AN:

86252

European-Finnish (FIN)

AF:

0.0538

AC:

2826

AN:

52552

Middle Eastern (MID)

AF:

0.105

AC:

605

AN:

5768

European-Non Finnish (NFE)

AF:

0.0814

AC:

90500

AN:

1111938

Other (OTH)

AF:

0.0978

AC:

5905

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

7567

15134

22701

30268

37835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3396

6792

10188

13584

16980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.101

AC:

15346

AN:

152204

Hom.:

858

Cov.:

AF XY:

0.0993

AC XY:

7389

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.138

AC:

5732

AN:

41500

American (AMR)

AF:

0.0802

AC:

1227

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

602

AN:

3470

East Asian (EAS)

AF:

0.0367

AC:

190

AN:

5176

South Asian (SAS)

AF:

0.151

AC:

730

AN:

4826

European-Finnish (FIN)

AF:

0.0539

AC:

572

AN:

10612

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0862

AC:

5858

AN:

67996

Other (OTH)

AF:

0.120

AC:

254

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

678

1357

2035

2714

3392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

352

528

704

880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0941

Hom.:

1519

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

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.00060

Eigen

Benign

0.036

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.82

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.54

PhyloP100

2.6

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.22

REVEL

Benign

0.040

Sift

Benign

0.21

Sift4G

Benign

0.31

Polyphen

0.12

Vest4

0.16

MutPred

0.14

Gain of sheet (P = 0.0827)

MPC

0.41

ClinPred

0.0047

GERP RS

3.6

PromoterAI

-0.019

Neutral

(source)

Varity_R

0.26

gMVP

0.28

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over