rs148319413

Variant names:

• chr6-31970423-C-A
• rs148319413
• NM_005510.4:c.868G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31970423-C-A
• chr6-31970423-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_005510.4(DXO):​c.868G>T​(p.Val290Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DXO NM_005510.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.954

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DXO	NM_005510.4	c.868G>T	p.Val290Phe	missense_variant	Exon 5 of 7	ENST00000337523.10	NP_005501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DXO	ENST00000337523.10	c.868G>T	p.Val290Phe	missense_variant	Exon 5 of 7	1	NM_005510.4	ENSP00000337759.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.063	T;T;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.84	D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.95	D;D;D
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.6	M;M;M
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.6	D;D;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.010	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.81
MutPred		0.86		Gain of catalytic residue at V290 (P = 0.1364);Gain of catalytic residue at V290 (P = 0.1364);Gain of catalytic residue at V290 (P = 0.1364);
MVP		0.65
MPC		1.3
ClinPred		0.98	D
GERP RS		4.2
Varity_R		0.46
gMVP		0.83

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: rs148319413; hg19: chr6-31938200;