6-31970674-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_005510.4(DXO):c.744A>G(p.Pro248=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0872 in 1,612,802 control chromosomes in the GnomAD database, including 7,142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (869 hom., cov: 32)
  • Exomes 𝑓: 0.086 (6273 hom.)
• Consequence: DXO NM_005510.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.95

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 6-31970674-T-C is Benign according to our data. Variant chr6-31970674-T-C is described in ClinVar as [Benign]. Clinvar id is 403445.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.95 with no splicing effect.
• 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.744A>G	p.Pro248=	synonymous_variant	4/7	ENST00000337523.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DXO	ENST00000337523.10	c.744A>G	p.Pro248=	synonymous_variant	4/7	1	NM_005510.4	P1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15404 AN: 151964 Hom.: 874 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.0805

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.0366

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0541

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0862

Gnomad OTH AF: 0.121

GnomAD3 exomes AF: 0.0898 AC: 22155 AN: 246806 Hom.: 1259 AF XY: 0.0916 AC XY: 12322 AN XY: 134448

Gnomad AFR exome AF: 0.150

Gnomad AMR exome AF: 0.0750

Gnomad ASJ exome AF: 0.180

Gnomad EAS exome AF: 0.0338

Gnomad SAS exome AF: 0.129

Gnomad FIN exome AF: 0.0538

Gnomad NFE exome AF: 0.0828

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.0858 AC: 125283 AN: 1460720 Hom.: 6273 Cov.: 34 AF XY: 0.0869 AC XY: 63141 AN XY: 726676

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.0784

Gnomad4 ASJ exome AF: 0.178

Gnomad4 EAS exome AF: 0.0213

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.0539

Gnomad4 NFE exome AF: 0.0814

Gnomad4 OTH exome AF: 0.0979

GnomAD4 genome AF: 0.101 AC: 15407 AN: 152082 Hom.: 869 Cov.: 32 AF XY: 0.0997 AC XY: 7415 AN XY: 74358

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.0803

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.0368

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.0541

Gnomad4 NFE AF: 0.0862

Gnomad4 OTH AF: 0.120

Alfa AF: 0.0938 Hom.: 483

Bravo AF: 0.107

Asia WGS AF: 0.0740 AC: 258 AN: 3478

EpiCase AF: 0.0980

EpiControl AF: 0.0945

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
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.73
Dann	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs35337578; hg19: chr6-31938451;