rs45442092

chr2-31372264-C-Gchr2-31372264-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000379.4(XDH):c.1820G>C(p.Arg607Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R607Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: XDH NM_000379.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.13

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XDH	NM_000379.4	c.1820G>C	p.Arg607Pro	missense_variant	17/36	ENST00000379416.4
XDH	XM_011533095.3	c.1817G>C	p.Arg606Pro	missense_variant	17/36
XDH	XM_011533096.3	c.1820G>C	p.Arg607Pro	missense_variant	17/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XDH	ENST00000379416.4	c.1820G>C	p.Arg607Pro	missense_variant	17/36	1	NM_000379.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251432 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135908

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.052
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0085	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	0.96	D
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.18
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.036	D
Polyphen		0.0040	B
Vest4		0.80
MutPred		0.54		Loss of MoRF binding (P = 0.0173);
MVP		0.53
MPC		0.050
ClinPred		0.84	D
GERP RS		5.2
Varity_R		0.96
gMVP		0.95

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

LitVar

Other links and lift over

dbSNP: rs45442092; hg19: chr2-31595130;