rs416002

Variant names:

• chr6-31970858-G-C
• rs416002
• ENST00000473976.1:n.1066C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000473976.1(DXO):​n.1066C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 1,612,010 control chromosomes in the GnomAD database, including 1,990 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.051 (288 hom., cov: 32)
  • Exomes 𝑓: 0.043 (1702 hom.)
• Consequence: DXO ENST00000473976.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.603
• Publications: 4 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]

STK19 (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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DXO	NM_005510.4	c.593-33C>G		intron_variant	Intron 3 of 6	ENST00000337523.10	NP_005501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DXO	ENST00000337523.10	c.593-33C>G		intron_variant	Intron 3 of 6	1	NM_005510.4	ENSP00000337759.5

Frequencies

GnomAD3 genomes AF: 0.0514 AC: 7821 AN: 152060 Hom.: 289 Cov.: 32

Gnomad AFR AF: 0.0984

Gnomad AMI AF: 0.0275

Gnomad AMR AF: 0.0520

Gnomad ASJ AF: 0.0136

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0401

Gnomad OTH AF: 0.0540

GnomAD2 exomes AF: 0.0298 AC: 7314 AN: 245334 AF XY: 0.0279

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.0365

Gnomad ASJ exome AF: 0.0122

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00414

Gnomad NFE exome AF: 0.0373

Gnomad OTH exome AF: 0.0377

GnomAD4 exome AF: 0.0428 AC: 62431 AN: 1459832 Hom.: 1702 Cov.: 34 AF XY: 0.0406 AC XY: 29491 AN XY: 726102

African (AFR) AF: 0.0976 AC: 3264 AN: 33444

American (AMR) AF: 0.0386 AC: 1724 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 348 AN: 26100

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39684

South Asian (SAS) AF: 0.000429 AC: 37 AN: 86252

European-Finnish (FIN) AF: 0.00486 AC: 254 AN: 52230

Middle Eastern (MID) AF: 0.00936 AC: 54 AN: 5768

European-Non Finnish (NFE) AF: 0.0488 AC: 54214 AN: 1111308

Other (OTH) AF: 0.0420 AC: 2534 AN: 60348

GnomAD4 genome AF: 0.0514 AC: 7828 AN: 152178 Hom.: 288 Cov.: 32 AF XY: 0.0484 AC XY: 3605 AN XY: 74412

African (AFR) AF: 0.0983 AC: 4077 AN: 41490

American (AMR) AF: 0.0520 AC: 795 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 47 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4820

European-Finnish (FIN) AF: 0.00264 AC: 28 AN: 10616

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0401 AC: 2728 AN: 67992

Other (OTH) AF: 0.0534 AC: 113 AN: 2116

Alfa AF: 0.0381 Hom.: 30

Bravo AF: 0.0591

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.9
DANN	Benign	0.65
PhyloP100		0.60
PromoterAI		-0.012	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs416002; hg19: chr6-31938635;