rs45551133

Positions:

• chr6-52984579-A-C
• chr6-52984579-A-G

Variant summary

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

The NM_001512.4(GSTA4):​c.299T>G​(p.Leu100Arg) variant causes a missense 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L100P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GSTA4 NM_001512.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319

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 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=0.069672495).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTA4	NM_001512.4	c.299T>G	p.Leu100Arg	missense_variant	5/7	ENST00000370963.9	NP_001503.1
GSTA4	XM_005249035.5	c.299T>G	p.Leu100Arg	missense_variant	5/7		XP_005249092.1
GSTA4	XM_011514534.4	c.188T>G	p.Leu63Arg	missense_variant	4/6		XP_011512836.1
GSTA4	XM_011514535.4	c.188T>G	p.Leu63Arg	missense_variant	4/6		XP_011512837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTA4	ENST00000370963.9	c.299T>G	p.Leu100Arg	missense_variant	5/7	1	NM_001512.4	ENSP00000360002	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T;.;T;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.31	N
LIST_S2	Uncertain	0.87	.;D;T;D
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.070	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.65	N;.;N;.
MutationTaster	Benign	0.87	D;D;D;D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.060	N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.63	T;T;T;T
Sift4G	Benign	0.48	T;T;T;T
Polyphen		0.0050	B;.;B;.
Vest4		0.21
MutPred		0.30		Loss of stability (P = 0.0537);.;Loss of stability (P = 0.0537);.;
MVP		0.13
MPC		0.62
ClinPred		0.80	D
GERP RS		5.0
Varity_R		0.33

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: rs45551133; hg19: chr6-52849377;