Genetic Variant DXO:c.593-33C>G (chr6-31970858-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005510.4(DXO):c.593-33C>G variant causes a intron 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
NM_005510.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.603

Publications

4 publications found

Variant links:

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]

DXO links:

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]

WHR1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_005510.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DXO	NM_005510.4	MANE Select	c.593-33C>G	intron	N/A	NP_005501.2
DXO	NM_001438478.1		c.593-33C>G	intron	N/A	NP_001425407.1
DXO	NM_001438479.1		c.593-33C>G	intron	N/A	NP_001425408.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DXO	ENST00000337523.10	TSL:1 MANE Select	c.593-33C>G	intron	N/A	ENSP00000337759.5	O77932
DXO	ENST00000375356.7	TSL:1	c.593-33C>G	intron	N/A	ENSP00000364505.3	O77932
DXO	ENST00000473976.1	TSL:1	n.1066C>G	non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.0514

AC:

7821

AN:

152060

Hom.:

289

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0406

AC XY:

29491

AN XY:

726102

show subpopulations

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:

AN:

39684

South Asian (SAS)

AF:

0.000429

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00486

AC:

254

AN:

52230

Middle Eastern (MID)

AF:

0.00936

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0488

AC:

54214

AN:

1111308

Other (OTH)

AF:

0.0420

AC:

2534

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

3929

7857

11786

15714

19643

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2188

4376

6564

8752

10940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0514

AC:

7828

AN:

152178

Hom.:

288

Cov.:

AF XY:

0.0484

AC XY:

3605

AN XY:

74412

show subpopulations

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:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00104

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00264

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0401

AC:

2728

AN:

67992

Other (OTH)

AF:

0.0534

AC:

113

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

388

775

1163

1550

1938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0381

Hom.:

Bravo

AF:

0.0591

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.9

(source)

DANN

Benign

0.65

PhyloP100

0.60

PromoterAI

-0.012

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over