6-52896870-C-G

Position:

• chr6-52896870-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000847.5(GSTA3):​c.605G>C​(p.Ser202Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00155 in 1,614,050 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (36 hom.)
• Consequence: GSTA3 NM_000847.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.86

Genes affected

GSTA3 (HGNC:4628): (glutathione S-transferase alpha 3) 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 genes that are located in a cluster mapped to chromosome 6. Genes of the alpha class are highly related and encode enzymes with glutathione peroxidase activity. However, during evolution, this alpha class gene diverged accumulating mutations in the active site that resulted in differences in substrate specificity and catalytic activity. The enzyme encoded by this gene catalyzes the double bond isomerization of precursors for progesterone and testosterone during the biosynthesis of steroid hormones. An additional transcript variant has been identified, but its full length sequence has not been determined. [provided by RefSeq, Jul 2008]

LOC105375091 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004918754).
• BP6: Variant 6-52896870-C-G is Benign according to our data. Variant chr6-52896870-C-G is described in ClinVar as [Benign]. Clinvar id is 728744.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00159 (2331/1461732) while in subpopulation SAS AF= 0.0192 (1655/86198). AF 95% confidence interval is 0.0184. There are 36 homozygotes in gnomad4_exome. There are 1605 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTA3	NM_000847.5	c.605G>C	p.Ser202Thr	missense_variant	7/7	ENST00000211122.4	NP_000838.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTA3	ENST00000211122.4	c.605G>C	p.Ser202Thr	missense_variant	7/7	1	NM_000847.5	ENSP00000211122.3
GSTA3	ENST00000370968.5	c.455G>C	p.Ser152Thr	missense_variant	6/6	1		ENSP00000360007.1

Frequencies

GnomAD3 genomes AF: 0.00108 AC: 165 AN: 152200 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00324 AC: 814 AN: 251394 Hom.: 14 AF XY: 0.00419 AC XY: 569 AN XY: 135868

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00246

Gnomad ASJ exome AF: 0.00635

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0191

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000475

Gnomad OTH exome AF: 0.00407

GnomAD4 exome AF: 0.00159 AC: 2331 AN: 1461732 Hom.: 36 Cov.: 30 AF XY: 0.00221 AC XY: 1605 AN XY: 727162

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00221

Gnomad4 ASJ exome AF: 0.00566

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0192

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000260

Gnomad4 OTH exome AF: 0.00179

GnomAD4 genome AF: 0.00108 AC: 165 AN: 152318 Hom.: 2 Cov.: 32 AF XY: 0.00153 AC XY: 114 AN XY: 74474

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00110 Hom.: 0

Bravo AF: 0.000827

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.00356 AC: 432

Asia WGS AF: 0.00693 AC: 25 AN: 3478

EpiCase AF: 0.000763

EpiControl AF: 0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	.;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.97	D;D
MetaRNN	Benign	0.0049	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	4.0	.;H
PrimateAI	Uncertain	0.48	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.19
Sift	Uncertain	0.026	D;D
Sift4G	Uncertain	0.035	D;D
Polyphen		1.0	.;D
Vest4		0.32
MVP		0.32
MPC		0.037
ClinPred		0.12	T
GERP RS		3.3
Varity_R		0.69
gMVP		0.22

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: rs149910347; hg19: chr6-52761668;