6-31971440-C-T

Variant names:

• chr6-31971440-C-T
• rs958774028
• NM_005510.4:c.236G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005510.4(DXO):​c.236G>A​(p.Gly79Asp) 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 benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DXO NM_005510.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.31
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08440146).

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.236G>A	p.Gly79Asp	missense	Exon 2 of 7	NP_005501.2
	DXO	NM_001438478.1		c.236G>A	p.Gly79Asp	missense	Exon 1 of 6	NP_001425407.1
	DXO	NM_001438479.1		c.236G>A	p.Gly79Asp	missense	Exon 2 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.236G>A	p.Gly79Asp	missense	Exon 2 of 7	ENSP00000337759.5	O77932
	DXO	ENST00000375356.7	TSL:1	c.236G>A	p.Gly79Asp	missense	Exon 1 of 6	ENSP00000364505.3	O77932
	WHR1	ENST00000466132.6	TSL:1	c.-544+166C>T		intron	N/A	ENSP00000519788.1	P49842-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.00027	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.38	N
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.3
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.041
Sift	Benign	0.60	T
Sift4G	Benign	0.45	T
Polyphen		0.0080	B
Vest4		0.19
MutPred		0.20		Loss of glycosylation at P74 (P = 0.0968)
MVP		0.34
MPC		0.48
ClinPred		0.16	T
GERP RS		4.1
PromoterAI		-0.035	Neutral
Varity_R		0.096
gMVP		0.54
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs958774028; hg19: chr6-31939217;