rs771818589

Variant names:

• chr6-52836305-G-A
• rs771818589
• ENST00000370989.6:c.203C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-52836305-G-A
• chr6-52836305-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_153699.3(GSTA5):​c.203C>T​(p.Thr68Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. T68N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GSTA5 NM_153699.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.48

Genes affected

GSTA5 (HGNC:19662): (glutathione S-transferase alpha 5) The glutathione S-transferases (GST; EC 2.5.1.18) catalyze the conjugation of reduced glutathiones and a variety of electrophiles, including many known carcinogens and mutagens. The cytosolic GSTs belong to a large superfamily, with members located on different chromosomes. For additional information on GSTs, see GSTA1 (MIM 138359).[supplied by OMIM, Sep 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.888

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTA5	NM_153699.3	c.203C>T	p.Thr68Ile	missense_variant	Exon 3 of 6		NP_714543.1
GSTA5	XM_054328422.1	c.203C>T	p.Thr68Ile	missense_variant	Exon 4 of 7		XP_054184397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTA5	ENST00000370989.6	c.203C>T	p.Thr68Ile	missense_variant	Exon 3 of 6	1		ENSP00000360028.1
GSTA5	ENST00000475052.1	n.169+1253C>T		intron_variant	Intron 2 of 4	5		ENSP00000518828.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461436 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727080

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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	0.56
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T;T
Eigen	Uncertain	0.40
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.91	.;D
M_CAP	Benign	0.0060	T
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.7	H;H
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.0	D;D
REVEL	Benign	0.22
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.013	D;D
Polyphen		0.99	D;D
Vest4		0.78
MutPred		0.76		Gain of MoRF binding (P = 0.1242);Gain of MoRF binding (P = 0.1242);
MVP		0.23
MPC		0.047
ClinPred		0.98	D
GERP RS		1.7
Varity_R		0.35
gMVP		0.39

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: rs771818589; hg19: chr6-52701103;