6-31970635-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.62

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]

ACMG classification

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	UniProt
DXO	NM_005510.4	c.783C>A	p.His261Gln	missense_variant	4/7	ENST00000337523.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DXO	ENST00000337523.10	c.783C>A	p.His261Gln	missense_variant	4/7	1	NM_005510.4	P1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15343 AN: 152086 Hom.: 863 Cov.: 32

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

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.: 34 AF XY: 0.0868 AC XY: 63078 AN XY: 726774

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.: 32 AF XY: 0.0993 AC XY: 7389 AN XY: 74414

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

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	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	18
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	D
MetaRNN	Benign	0.0015	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.54	N;N;N
MutationTaster	Benign	0.13	P;P;P
PrimateAI	Uncertain	0.51	T
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	T
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

Other links and lift over

dbSNP: rs17207867; hg19: chr6-31938412;