3-49026573-TAT-ATA

Variant names:

• chr3-49026573-TAT-ATA
• NM_000884.3:c.854_856delATAinsTAT

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000884.3(IMPDH2):​c.854_856delATAinsTAT​(p.AsnMet285IleLeu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: IMPDH2 NM_000884.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.92

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPDH2	NM_000884.3	c.854_856delATAinsTAT	p.AsnMet285IleLeu	missense_variant		ENST00000326739.9	NP_000875.2
IMPDH2	NM_001410759.1	c.854_856delATAinsTAT	p.AsnMet285IleLeu	missense_variant			NP_001397688.1
IMPDH2	NM_001410760.1	c.779_781delATAinsTAT	p.AsnMet260IleLeu	missense_variant			NP_001397689.1
IMPDH2	NM_001410761.1	c.779_781delATAinsTAT	p.AsnMet260IleLeu	missense_variant			NP_001397690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMPDH2	ENST00000326739.9	c.854_856delATAinsTAT	p.AsnMet285IleLeu	missense_variant		1	NM_000884.3	ENSP00000321584.4
ENSG00000290315	ENST00000703936.1	c.2894_2896delATAinsTAT	p.AsnMet965IleLeu	missense_variant				ENSP00000515567.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

May 11, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of 2 amino acids and insertion of 2 incorrect amino acids in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr3-49064006;