11-67585320-TC-CA

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_000852.4(GSTP1):c.336+79_336+80delinsCA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GSTP1 NM_000852.4 intron
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.320

Genes affected

GSTP1 (HGNC:4638): (glutathione S-transferase pi 1) Glutathione S-transferases (GSTs) are a family of enzymes that play an important role in detoxification by catalyzing the conjugation of many hydrophobic and electrophilic compounds with reduced glutathione. Based on their biochemical, immunologic, and structural properties, the soluble GSTs are categorized into 4 main classes: alpha, mu, pi, and theta. This GST family member is a polymorphic gene encoding active, functionally different GSTP1 variant proteins that are thought to function in xenobiotic metabolism and play a role in susceptibility to cancer, and other diseases. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-67585320-TC-CA is Pathogenic according to our data. Variant chr11-67585320-TC-CA is described in ClinVar as [Likely_pathogenic]. Clinvar id is 496691.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTP1	NM_000852.4	c.336+79_336+80delinsCA		intron_variant		ENST00000398606.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTP1	ENST00000398606.10	c.336+79_336+80delinsCA		intron_variant		1	NM_000852.4	P1

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: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Kala-azar susceptibility 2 Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Research Laboratory, University Department of Zoology, Vinoba Bhave University

Sep 14, 2017

Novel Mutation Observed i.e. Change in Coding frame (Ser122Gln) and in nucleotide (TC to CA) in Exon-5 of GSTP1 gene in Clinical Isolates of Visceral Leishmaniasis from Endemic Population of India has certainly a clinical relevance. We have yet to ascertain the exact functional and clinical relevance but we found two important finding in terms of clinical significance. Firstly, observed frame shift mutation (changing the protein sequence (S to Q amino acid) and also double mutation in nucleotide i.e. TC to CA position in addition to investigated and known mutation Ile105Val (G to A) and have shown very strong genetic association (OR=5.1; p=0.008) with primary infection and reasonably strong genetic association (OR=3.2; p=0.04) with relapse infection in endemic population. However, we are in a process to investigate in larger sample size. Secondly, this observation may serve as clinico-epidemiological marker for prospective diagnostic marker in due course of time in addition to existing molecular markers. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555022268; hg19: chr11-67352791;