6-31971004-G-T

Variant names:

• chr6-31971004-G-T
• rs780110626
• NM_005510.4:c.500C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005510.4(DXO):​c.500C>A​(p.Thr167Lys) variant causes a missense change involving the alteration of a 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T167I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DXO NM_005510.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.10
• 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]

WHR1 (HGNC:11398): (serine/threonine kinase 19) This gene encodes a serine/threonine kinase which localizes predominantly to the nucleus. Its specific function is unknown; it is possible that phosphorylation of this protein is involved in transcriptional regulation. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6 and expresses two transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.811

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.500C>A	p.Thr167Lys	missense	Exon 3 of 7	NP_005501.2
	DXO	NM_001438478.1		c.500C>A	p.Thr167Lys	missense	Exon 2 of 6	NP_001425407.1
	DXO	NM_001438479.1		c.500C>A	p.Thr167Lys	missense	Exon 3 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.500C>A	p.Thr167Lys	missense	Exon 3 of 7	ENSP00000337759.5	O77932
	DXO	ENST00000375356.7	TSL:1	c.500C>A	p.Thr167Lys	missense	Exon 2 of 6	ENSP00000364505.3	O77932
	DXO	ENST00000473976.1	TSL:1	n.920C>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000406 AC: 1 AN: 246558 AF XY: 0.00000744

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000847 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.075	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.97	D
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		9.1
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.089	T
Polyphen		1.0	D
Vest4		0.74
MutPred		0.42		Gain of ubiquitination at T167 (P = 0.0104)
MVP		0.64
MPC		1.3
ClinPred		0.95	D
GERP RS		5.2
PromoterAI		0.021	Neutral
Varity_R		0.43
gMVP		0.89
Mutation Taster		=25/75	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs780110626; hg19: chr6-31938781;