rs1167228380

Variant names:

• chr6-31970974-C-T
• rs1167228380
• NM_005510.4:c.530G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-31970974-C-T
• chr6-31970974-C-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.530G>A​(p.Arg177Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,460,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R177W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: DXO NM_005510.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.45
• Publications: 1 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=0.22540236).

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.530G>A	p.Arg177Gln	missense	Exon 3 of 7	NP_005501.2
	DXO	NM_001438478.1		c.530G>A	p.Arg177Gln	missense	Exon 2 of 6	NP_001425407.1
	DXO	NM_001438479.1		c.530G>A	p.Arg177Gln	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.530G>A	p.Arg177Gln	missense	Exon 3 of 7	ENSP00000337759.5	O77932
	DXO	ENST00000375356.7	TSL:1	c.530G>A	p.Arg177Gln	missense	Exon 2 of 6	ENSP00000364505.3	O77932
	DXO	ENST00000473976.1	TSL:1	n.950G>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1460746 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 726694

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112000

Other (OTH) AF: 0.0000166 AC: 1 AN: 60386

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 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	0.098
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.00086	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.4
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.10
Sift	Benign	0.22	T
Sift4G	Benign	0.21	T
Polyphen		0.91	P
Vest4		0.29
MVP		0.33
MPC		0.53
ClinPred		0.89	D
GERP RS		5.2
PromoterAI		0.0076	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.74
Mutation Taster		=65/35	polymorphism

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: rs1167228380; hg19: chr6-31938751;