6-31970674-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_005510.4(DXO):​c.744A>C​(p.Pro248Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P248P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DXO NM_005510.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.95
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.096).
• BP7: Synonymous conserved (PhyloP=-2.95 with no splicing effect.

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>C	p.Pro248Pro	synonymous	Exon 4 of 7	NP_005501.2
	DXO	NM_001438478.1		c.744A>C	p.Pro248Pro	synonymous	Exon 3 of 6	NP_001425407.1
	DXO	NM_001438479.1		c.744A>C	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>C	p.Pro248Pro	synonymous	Exon 4 of 7	ENSP00000337759.5	O77932
	DXO	ENST00000375356.7	TSL:1	c.744A>C	p.Pro248Pro	synonymous	Exon 3 of 6	ENSP00000364505.3	O77932
	DXO	ENST00000473976.1	TSL:1	n.1250A>C		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.41
DANN	Benign	0.65
PhyloP100		-3.0
PromoterAI		0.0056	Neutral
Mutation Taster		=100/0	polymorphism

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: rs35337578; hg19: chr6-31938451;