6-31970674-T-C

Variant names:

• chr6-31970674-T-C
• rs35337578
• NM_005510.4:c.744A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_005510.4(DXO):​c.744A>G​(p.Pro248Pro) 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
• Publications: 5 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.096).
• BP6: Variant 6-31970674-T-C is Benign according to our data. Variant chr6-31970674-T-C is described in ClinVar as Benign. ClinVar VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DXO	NM_005510.4	MANE Select	c.744A>G	p.Pro248Pro	synonymous	Exon 4 of 7	NP_005501.2
	DXO	NM_001438478.1		c.744A>G	p.Pro248Pro	synonymous	Exon 3 of 6	NP_001425407.1
	DXO	NM_001438479.1		c.744A>G	p.Pro248Pro	synonymous	Exon 4 of 7	NP_001425408.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DXO	ENST00000337523.10	TSL:1 MANE Select	c.744A>G	p.Pro248Pro	synonymous	Exon 4 of 7	ENSP00000337759.5	O77932
	DXO	ENST00000375356.7	TSL:1	c.744A>G	p.Pro248Pro	synonymous	Exon 3 of 6	ENSP00000364505.3	O77932
	DXO	ENST00000473976.1	TSL:1	n.1250A>G		non_coding_transcript_exon	Exon 2 of 3

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

GnomAD2 exomes AF: 0.0898 AC: 22155 AN: 246806 AF XY: 0.0916

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 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

African (AFR) AF: 0.152 AC: 5075 AN: 33478

American (AMR) AF: 0.0784 AC: 3505 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 4664 AN: 26134

East Asian (EAS) AF: 0.0213 AC: 845 AN: 39700

South Asian (SAS) AF: 0.131 AC: 11294 AN: 86252

European-Finnish (FIN) AF: 0.0539 AC: 2818 AN: 52302

Middle Eastern (MID) AF: 0.105 AC: 605 AN: 5768

European-Non Finnish (NFE) AF: 0.0814 AC: 90568 AN: 1111978

Other (OTH) AF: 0.0979 AC: 5909 AN: 60386

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

African (AFR) AF: 0.140 AC: 5790 AN: 41456

American (AMR) AF: 0.0803 AC: 1228 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 604 AN: 3472

East Asian (EAS) AF: 0.0368 AC: 190 AN: 5158

South Asian (SAS) AF: 0.151 AC: 730 AN: 4820

European-Finnish (FIN) AF: 0.0541 AC: 574 AN: 10604

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0862 AC: 5857 AN: 67962

Other (OTH) AF: 0.120 AC: 253 AN: 2112

Alfa AF: 0.0926 Hom.: 1614

Bravo AF: 0.107

Asia WGS AF: 0.0740 AC: 258 AN: 3478

EpiCase AF: 0.0980

EpiControl AF: 0.0945

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.73
DANN	Benign	0.62
PhyloP100		-3.0
PromoterAI		-0.025	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35337578; hg19: chr6-31938451;