rs2287395

Variant names:

• chr14-77325176-A-G
• rs2287395
• NM_145870.3:c.67+255A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145870.3(GSTZ1):​c.67+255A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 490,296 control chromosomes in the GnomAD database, including 23,534 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.30 (6992 hom., cov: 32)
  • Exomes 𝑓: 0.30 (16542 hom.)
• Consequence: GSTZ1 NM_145870.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758
• Publications: 12 publications found

Genes affected

GSTZ1 (HGNC:4643): (glutathione S-transferase zeta 1) This gene is a member of the glutathione S-transferase (GSTs) super-family which encodes multifunctional enzymes important in the detoxification of electrophilic molecules, including carcinogens, mutagens, and several therapeutic drugs, by conjugation with glutathione. This enzyme catalyzes the conversion of maleylacetoacetate to fumarylacetoacatate, which is one of the steps in the phenylalanine/tyrosine degradation pathway. Deficiency of a similar gene in mouse causes oxidative stress. Several transcript variants of this gene encode multiple protein isoforms. [provided by RefSeq, Jul 2015]

GSTZ1 Gene-Disease associations (from GenCC):

• maleylacetoacetate isomerase deficiency

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTZ1	NM_145870.3	c.67+255A>G		intron_variant	Intron 2 of 8	ENST00000216465.10	NP_665877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTZ1	ENST00000216465.10	c.67+255A>G		intron_variant	Intron 2 of 8	1	NM_145870.3	ENSP00000216465.5

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45521 AN: 152014 Hom.: 6977 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.264

GnomAD4 exome AF: 0.304 AC: 102736 AN: 338164 Hom.: 16542 Cov.: 0 AF XY: 0.296 AC XY: 52697 AN XY: 178256

African (AFR) AF: 0.301 AC: 3078 AN: 10238

American (AMR) AF: 0.201 AC: 3110 AN: 15466

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 2886 AN: 10118

East Asian (EAS) AF: 0.475 AC: 10953 AN: 23038

South Asian (SAS) AF: 0.180 AC: 6895 AN: 38372

European-Finnish (FIN) AF: 0.382 AC: 7960 AN: 20850

Middle Eastern (MID) AF: 0.172 AC: 250 AN: 1452

European-Non Finnish (NFE) AF: 0.310 AC: 61663 AN: 199068

Other (OTH) AF: 0.304 AC: 5941 AN: 19562

GnomAD4 genome AF: 0.299 AC: 45557 AN: 152132 Hom.: 6992 Cov.: 32 AF XY: 0.298 AC XY: 22188 AN XY: 74366

African (AFR) AF: 0.299 AC: 12389 AN: 41492

American (AMR) AF: 0.212 AC: 3244 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 972 AN: 3472

East Asian (EAS) AF: 0.439 AC: 2266 AN: 5164

South Asian (SAS) AF: 0.194 AC: 936 AN: 4818

European-Finnish (FIN) AF: 0.378 AC: 4003 AN: 10580

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20844 AN: 67990

Other (OTH) AF: 0.271 AC: 573 AN: 2114

Alfa AF: 0.291 Hom.: 10213

Bravo AF: 0.289

Asia WGS AF: 0.325 AC: 1126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.1
DANN	Benign	0.69
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2287395; hg19: chr14-77791519;