3-49026719-G-C

Variant names:

• chr3-49026719-G-C
• NM_000884.3:c.787C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000884.3(IMPDH2):​c.787C>G​(p.Leu263Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IMPDH2 NM_000884.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.50

Genes affected

IMPDH2 (HGNC:6053): (inosine monophosphate dehydrogenase 2) This gene encodes the rate-limiting enzyme in the de novo guanine nucleotide biosynthesis. It is thus involved in maintaining cellular guanine deoxy- and ribonucleotide pools needed for DNA and RNA synthesis. The encoded protein catalyzes the NAD-dependent oxidation of inosine-5'-monophosphate into xanthine-5'-monophosphate, which is then converted into guanosine-5'-monophosphate. This gene is up-regulated in some neoplasms, suggesting it may play a role in malignant transformation. [provided by RefSeq, Jul 2008]

ENSG00000290315 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.916

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPDH2	NM_000884.3	c.787C>G	p.Leu263Val	missense_variant	Exon 7 of 14	ENST00000326739.9	NP_000875.2
IMPDH2	NM_001410759.1	c.787C>G	p.Leu263Val	missense_variant	Exon 7 of 15		NP_001397688.1
IMPDH2	NM_001410760.1	c.712C>G	p.Leu238Val	missense_variant	Exon 6 of 14		NP_001397689.1
IMPDH2	NM_001410761.1	c.712C>G	p.Leu238Val	missense_variant	Exon 6 of 13		NP_001397690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMPDH2	ENST00000326739.9	c.787C>G	p.Leu263Val	missense_variant	Exon 7 of 14	1	NM_000884.3	ENSP00000321584.4
ENSG00000290315	ENST00000703936.1	c.2827C>G	p.Leu943Val	missense_variant	Exon 15 of 22			ENSP00000515567.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.85	D;.
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.92	D;D
MetaSVM	Uncertain	0.78	D
MutationAssessor	Pathogenic	4.1	H;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.013	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		1.0	D;.
Vest4		0.89
MutPred		0.80		Gain of glycosylation at Y258 (P = 0.0838);.;
MVP		0.94
MPC		0.96
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.88
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-49064152;