6-52902401-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000847.5(GSTA3):c.217A>G(p.Asn73Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0102 in 1,614,006 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0077 (6 hom., cov: 32)
  • Exomes 𝑓: 0.010 (116 hom.)
• Consequence: GSTA3 NM_000847.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.24

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012420088).
• BP6: Variant 6-52902401-T-C is Benign according to our data. Variant chr6-52902401-T-C is described in ClinVar as [Benign]. Clinvar id is 774447.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTA3	NM_000847.5	c.217A>G	p.Asn73Asp	missense_variant	4/7	ENST00000211122.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTA3	ENST00000211122.4	c.217A>G	p.Asn73Asp	missense_variant	4/7	1	NM_000847.5	P1
GSTA3	ENST00000370968.5	c.67A>G	p.Asn23Asp	missense_variant	3/6	1
GSTA3	ENST00000431899.2	c.67A>G	p.Asn23Asp	missense_variant	2/4	5

Frequencies

GnomAD3 genomes AF: 0.00770 AC: 1172 AN: 152186 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00655

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00850

Gnomad FIN AF: 0.00678

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0126

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00799 AC: 2010 AN: 251432 Hom.: 18 AF XY: 0.00823 AC XY: 1119 AN XY: 135884

Gnomad AFR exome AF: 0.00185

Gnomad AMR exome AF: 0.00489

Gnomad ASJ exome AF: 0.00238

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00915

Gnomad FIN exome AF: 0.00591

Gnomad NFE exome AF: 0.0118

Gnomad OTH exome AF: 0.00684

GnomAD4 exome AF: 0.0104 AC: 15254 AN: 1461702 Hom.: 116 Cov.: 31 AF XY: 0.0103 AC XY: 7481 AN XY: 727148

Gnomad4 AFR exome AF: 0.00155

Gnomad4 AMR exome AF: 0.00512

Gnomad4 ASJ exome AF: 0.00230

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00828

Gnomad4 FIN exome AF: 0.00599

Gnomad4 NFE exome AF: 0.0120

Gnomad4 OTH exome AF: 0.00826

GnomAD4 genome AF: 0.00770 AC: 1172 AN: 152304 Hom.: 6 Cov.: 32 AF XY: 0.00755 AC XY: 562 AN XY: 74460

Gnomad4 AFR AF: 0.00197

Gnomad4 AMR AF: 0.00654

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00850

Gnomad4 FIN AF: 0.00678

Gnomad4 NFE AF: 0.0126

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.0103 Hom.: 5

Bravo AF: 0.00680

TwinsUK AF: 0.0102 AC: 38

ALSPAC AF: 0.0119 AC: 46

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.0120 AC: 103

ExAC AF: 0.00826 AC: 1003

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.0109

EpiControl AF: 0.0108

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

Invitae

May 19, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.54
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.94	D;D;D
MetaRNN	Benign	0.012	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.75	N;N
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.5	D;D;D
REVEL	Benign	0.11
Sift	Uncertain	0.0090	D;D;D
Sift4G	Uncertain	0.026	D;T;.
Polyphen		0.99	.;D;.
Vest4		0.39
MVP		0.35
MPC		0.19
ClinPred		0.020	T
GERP RS		4.2
Varity_R		0.78
gMVP		0.43

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: rs41273858; hg19: chr6-52767199;