6-52832861-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000370989.7(GSTA5):c.544A>G(p.Lys182Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GSTA5 ENST00000370989.7 missense, splice_region
• Scores: Splicing: ADA: 0.001337
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20774117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTA5	NM_153699.3	c.544A>G	p.Lys182Glu	missense_variant, splice_region_variant	5/6	ENST00000370989.7
GSTA5	XM_054328422.1	c.544A>G	p.Lys182Glu	missense_variant, splice_region_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTA5	ENST00000370989.7	c.544A>G	p.Lys182Glu	missense_variant, splice_region_variant	5/6	1	NM_153699.3	P1
GSTA5	ENST00000475052.2	c.*246A>G		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	4/5	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2023

The c.544A>G (p.K182E) alteration is located in exon 6 (coding exon 5) of the GSTA5 gene. This alteration results from a A to G substitution at nucleotide position 544, causing the lysine (K) at amino acid position 182 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	21
Dann	Benign	0.94
DEOGEN2	Benign	0.010	T;T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.36	N
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.3	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.48	N;N
REVEL	Benign	0.24
Sift	Benign	0.062	T;T
Sift4G	Uncertain	0.018	D;D
Polyphen		0.0010	B;B
Vest4		0.40
MutPred		0.56		Loss of MoRF binding (P = 0.0189);Loss of MoRF binding (P = 0.0189);
MVP		0.23
MPC		0.023
ClinPred		0.96	D
GERP RS		-2.6
Varity_R		0.10
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0013
dbscSNV1_RF	Benign	0.18
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-52697659;