6-52984579-A-G

Variant names:

• chr6-52984579-A-G
• rs45551133
• NM_001512.4:c.299T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001512.4(GSTA4):​c.299T>C​(p.Leu100Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,613,716 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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: 𝑓 0.00098 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (1 hom.)
• Consequence: GSTA4 NM_001512.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319
• Publications: 8 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.017355025).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001512.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTA4	NM_001512.4	MANE Select	c.299T>C	p.Leu100Pro	missense	Exon 5 of 7	NP_001503.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTA4	ENST00000370963.9	TSL:1 MANE Select	c.299T>C	p.Leu100Pro	missense	Exon 5 of 7	ENSP00000360002.4
	GSTA4	ENST00000370959.1	TSL:5	c.299T>C	p.Leu100Pro	missense	Exon 5 of 7	ENSP00000359998.1
	GSTA4	ENST00000370960.5	TSL:3	c.20T>C	p.Leu7Pro	missense	Exon 2 of 4	ENSP00000359999.1

Frequencies

GnomAD3 genomes AF: 0.000979 AC: 149 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00171

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00100 AC: 252 AN: 251308 AF XY: 0.00104

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.00177

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.00143

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00123 AC: 1804 AN: 1461438 Hom.: 1 Cov.: 31 AF XY: 0.00123 AC XY: 892 AN XY: 727070

African (AFR) AF: 0.000269 AC: 9 AN: 33468

American (AMR) AF: 0.00204 AC: 91 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.000459 AC: 12 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86230

European-Finnish (FIN) AF: 0.000168 AC: 9 AN: 53416

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00145 AC: 1608 AN: 1111658

Other (OTH) AF: 0.00114 AC: 69 AN: 60372

GnomAD4 genome AF: 0.000978 AC: 149 AN: 152278 Hom.: 0 Cov.: 32 AF XY: 0.000913 AC XY: 68 AN XY: 74452

African (AFR) AF: 0.000168 AC: 7 AN: 41568

American (AMR) AF: 0.00118 AC: 18 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10596

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00171 AC: 116 AN: 68018

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.00129 Hom.: 0

Bravo AF: 0.00101

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000930 AC: 8

ExAC AF: 0.000914 AC: 111

EpiCase AF: 0.00174

EpiControl AF: 0.00166

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.22	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.32
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.13
Sift	Benign	0.25	T
Sift4G	Benign	0.23	T
Polyphen		0.98	D
Vest4		0.57
MVP		0.34
MPC		0.72
ClinPred		0.027	T
GERP RS		5.0
Varity_R		0.74
Mutation Taster		=69/31	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: rs45551133; hg19: chr6-52849377; COSMIC: COSV108890706;