6-52994220-G-A

Variant names:

• chr6-52994220-G-A
• rs754539343
• NM_001512.4:c.24C>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001512.4(GSTA4):​c.24C>T​(p.His8His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: GSTA4 NM_001512.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

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

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=1.6 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTA4	NM_001512.4	c.24C>T	p.His8His	synonymous_variant	Exon 2 of 7	ENST00000370963.9	NP_001503.1
GSTA4	XM_005249035.5	c.24C>T	p.His8His	synonymous_variant	Exon 2 of 7		XP_005249092.1
GSTA4	XM_011514534.4	c.-36C>T		5_prime_UTR_variant	Exon 2 of 6		XP_011512836.1
GSTA4	XM_011514535.4	c.-36C>T		5_prime_UTR_variant	Exon 2 of 6		XP_011512837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTA4	ENST00000370963.9	c.24C>T	p.His8His	synonymous_variant	Exon 2 of 7	1	NM_001512.4	ENSP00000360002.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs754539343; hg19: chr6-52859018;