rs2397118

Positions:

• chr6-52836345-C-G
• chr6-52836345-C-T

Variant summary

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

The ENST00000370989.7(GSTA5):​c.163G>C​(p.Val55Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. V55I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GSTA5 ENST00000370989.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.38

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTA5	NM_153699.3	c.163G>C	p.Val55Leu	missense_variant	3/6	ENST00000370989.7	NP_714543.1
GSTA5	XM_054328422.1	c.163G>C	p.Val55Leu	missense_variant	4/7		XP_054184397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTA5	ENST00000370989.7	c.163G>C	p.Val55Leu	missense_variant	3/6	1	NM_153699.3	ENSP00000360028	P1
GSTA5	ENST00000475052.2	c.139+1213G>C		intron_variant, NMD_transcript_variant		5		ENSP00000518828

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.92	.;D
M_CAP	Benign	0.0062	T
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L
MutationTaster	Benign	0.012	P;P
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.089
Sift	Benign	0.047	D;D
Sift4G	Benign	0.17	T;T
Polyphen		0.013	B;B
Vest4		0.38
MutPred		0.54		Gain of catalytic residue at V55 (P = 0.1623);Gain of catalytic residue at V55 (P = 0.1623);
MVP		0.21
MPC		0.013
ClinPred		0.88	D
GERP RS		2.6
Varity_R		0.24
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2397118; hg19: chr6-52701143;