rs4147617

Variant names:

• chr6-52982633-T-A
• rs4147617
• NM_001512.4:c.487A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-52982633-T-A
• chr6-52982633-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001512.4(GSTA4):​c.487A>T​(p.Thr163Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GSTA4 NM_001512.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 0 publications found

Genes affected

GSTA4 (HGNC:4629): (glutathione S-transferase alpha 4) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-tranferase belonging to the alpha class. The alpha class genes, which are located in a cluster on chromosome 6, are highly related and encode enzymes with glutathione peroxidase activity that function in the detoxification of lipid peroxidation products. Reactive electrophiles produced by oxidative metabolism have been linked to a number of degenerative diseases including Parkinson's disease, Alzheimer's disease, cataract formation, and atherosclerosis. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08689523).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTA4	NM_001512.4	c.487A>T	p.Thr163Ser	missense_variant	Exon 6 of 7	ENST00000370963.9	NP_001503.1
GSTA4	XM_005249035.5	c.487A>T	p.Thr163Ser	missense_variant	Exon 6 of 7		XP_005249092.1
GSTA4	XM_011514534.4	c.376A>T	p.Thr126Ser	missense_variant	Exon 5 of 6		XP_011512836.1
GSTA4	XM_011514535.4	c.376A>T	p.Thr126Ser	missense_variant	Exon 5 of 6		XP_011512837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTA4	ENST00000370963.9	c.487A>T	p.Thr163Ser	missense_variant	Exon 6 of 7	1	NM_001512.4	ENSP00000360002.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458096 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 725642

African (AFR) AF: 0.00 AC: 0 AN: 33416

American (AMR) AF: 0.0000224 AC: 1 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 86128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108676

Other (OTH) AF: 0.00 AC: 0 AN: 60268

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.071	T;.;T;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.049
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.70	.;T;T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.087	T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.77	N;.;N;.
PhyloP100		1.0
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.43	N;N;N;N
REVEL	Benign	0.069
Sift	Benign	0.47	T;T;T;T
Sift4G	Benign	0.48	T;T;T;T
Polyphen		0.0010	B;.;B;.
Vest4		0.10
MutPred		0.41		Loss of catalytic residue at T163 (P = 0.2471);.;Loss of catalytic residue at T163 (P = 0.2471);.;
MVP		0.18
MPC		0.11
ClinPred		0.25	T
GERP RS		4.1
Varity_R		0.16
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs4147617; hg19: chr6-52847431;