rs34929837

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000379.4(XDH):c.1184A>T(p.Lys395Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00404 in 1,614,144 control chromosomes in the GnomAD database, including 206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 93 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 113 hom. )

Consequence

XDH
NM_000379.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.789

Publications

8 publications found

Variant links:

Genes affected

XDH (HGNC:12805): (xanthine dehydrogenase) Xanthine dehydrogenase belongs to the group of molybdenum-containing hydroxylases involved in the oxidative metabolism of purines. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Xanthine dehydrogenase can be converted to xanthine oxidase by reversible sulfhydryl oxidation or by irreversible proteolytic modification. Defects in xanthine dehydrogenase cause xanthinuria, may contribute to adult respiratory stress syndrome, and may potentiate influenza infection through an oxygen metabolite-dependent mechanism. [provided by RefSeq, Jan 2014]

XDH Gene-Disease associations (from GenCC):

xanthinuria type I
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

XDH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006719202).

BP6

Variant 2-31379925-T-A is Benign according to our data. Variant chr2-31379925-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 335791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0665 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000379.4. 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
	XDH	NM_000379.4	MANE Select	c.1184A>T	p.Lys395Met	missense	Exon 13 of 36	NP_000370.2	P47989

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
XDH	ENST00000379416.4	TSL:1 MANE Select	c.1184A>T	p.Lys395Met	missense	Exon 13 of 36	ENSP00000368727.3	P47989
XDH	ENST00000879520.1		c.1292A>T	p.Lys431Met	missense	Exon 13 of 36	ENSP00000549579.1
XDH	ENST00000879524.1		c.1184A>T	p.Lys395Met	missense	Exon 13 of 36	ENSP00000549583.1

Frequencies

GnomAD3 genomes

AF:

0.0200

AC:

3040

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0687

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00792

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.0125

GnomAD2 exomes

AF:

0.00544

AC:

1367

AN:

251474

AF XY:

0.00383

show subpopulations

Gnomad AFR exome

AF:

0.0704

Gnomad AMR exome

AF:

0.00309

Gnomad ASJ exome

AF:

0.00546

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000387

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00238

AC:

3480

AN:

1461836

Hom.:

113

Cov.:

AF XY:

0.00205

AC XY:

1491

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.0750

AC:

2512

AN:

33478

American (AMR)

AF:

0.00342

AC:

153

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00524

AC:

137

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000151

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00348

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.000269

AC:

299

AN:

1111998

Other (OTH)

AF:

0.00573

AC:

346

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

193

387

580

774

967

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0200

AC:

3043

AN:

152308

Hom.:

Cov.:

AF XY:

0.0192

AC XY:

1428

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0686

AC:

2852

AN:

41566

American (AMR)

AF:

0.00797

AC:

122

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00403

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000382

AC:

AN:

68024

Other (OTH)

AF:

0.0123

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

144

288

432

576

720

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.00372

Hom.:

Bravo

AF:

0.0237

ESP6500AA

AF:

0.0660

AC:

291

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00648

AC:

787

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.000593

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary xanthinuria type 1 (2)

not provided (2)

Xanthinuria type II (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.0067

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.4

PhyloP100

0.79

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.21

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0090

Polyphen

0.97

Vest4

0.52

MVP

0.55

MPC

0.24

ClinPred

0.045

GERP RS

0.73

Varity_R

0.53

gMVP

0.76

Mutation Taster

=85/15

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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