NM_005510.4:c.783C>A

Variant names:

• chr6-31970635-G-T
• rs17207867
• NM_005510.4:c.783C>A

Variant summary

Our verdict is Benign. The variant received -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. 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.62
• Publications: 18 publications found

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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DXO	NM_005510.4	c.783C>A	p.His261Gln	missense_variant	Exon 4 of 7	ENST00000337523.10	NP_005501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DXO	ENST00000337523.10	c.783C>A	p.His261Gln	missense_variant	Exon 4 of 7	1	NM_005510.4	ENSP00000337759.5

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

GnomAD2 exomes AF: 0.0897 AC: 22224 AN: 247692 AF XY: 0.0916

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

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

GnomAD4 genome AF: 0.101 AC: 15346 AN: 152204 Hom.: 858 Cov.: 32 AF XY: 0.0993 AC XY: 7389 AN XY: 74414

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: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0862 AC: 5858 AN: 67996

Other (OTH) AF: 0.120 AC: 254 AN: 2116

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

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 v4.3

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
PhyloP100		2.6
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
PromoterAI		-0.019	Neutral
Varity_R		0.26
gMVP		0.28
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17207867; hg19: chr6-31938412;