rs45506591

chr11-67584521-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000852.4(GSTP1):c.95A>T(p.Glu32Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,584,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: GSTP1 NM_000852.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0759837).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTP1	NM_000852.4	c.95A>T	p.Glu32Val	missense_variant	3/7	ENST00000398606.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTP1	ENST00000398606.10	c.95A>T	p.Glu32Val	missense_variant	3/7	1	NM_000852.4	P1

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152044 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000145 AC: 29 AN: 200514 Hom.: 0 AF XY: 0.000147 AC XY: 16 AN XY: 109198

Gnomad AFR exome AF: 0.0000886

Gnomad AMR exome AF: 0.000107

Gnomad ASJ exome AF: 0.000881

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000184

Gnomad OTH exome AF: 0.000192

GnomAD4 exome AF: 0.000195 AC: 280 AN: 1432790 Hom.: 0 Cov.: 31 AF XY: 0.000204 AC XY: 145 AN XY: 710880

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000258

Gnomad4 ASJ exome AF: 0.000508

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000236

Gnomad4 OTH exome AF: 0.000118

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152044 Hom.: 0 Cov.: 33 AF XY: 0.0000943 AC XY: 7 AN XY: 74260

Gnomad4 AFR AF: 0.0000966

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000268 Hom.: 0

Bravo AF: 0.000166

ESP6500AA AF: 0.000258 AC: 1

ESP6500EA AF: 0.000121 AC: 1

ExAC AF: 0.0000838 AC: 10

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.43
Cadd	Uncertain	24
Dann	Uncertain	0.98
DEOGEN2	Benign	0.18	T;.;T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.062
FATHMM_MKL	Uncertain	0.78	D
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.076	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;.;L
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-4.1	D;D;.
REVEL	Benign	0.081
Sift	Benign	0.12	T;T;.
Polyphen		0.039	B;.;B
Vest4		0.40
MVP		0.64
MPC		0.039
ClinPred		0.063	T
GERP RS		5.1
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		4.0
Varity_R		0.65
gMVP		0.29

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: rs45506591; hg19: chr11-67351992; COSMIC: COSV101282055; COSMIC: COSV101282055;