rs2287397

Variant names:

• chr14-77330568-T-A
• rs2287397
• NM_145870.3:c.524+209T>A

Variant summary

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

The NM_145870.3(GSTZ1):​c.524+209T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 152,224 control chromosomes in the GnomAD database, including 53 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 0.019 (53 hom., cov: 32)
• Consequence: GSTZ1 NM_145870.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0508 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145870.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTZ1	NM_145870.3	MANE Select	c.524+209T>A		intron	N/A	NP_665877.1	A0A0C4DFM0
	GSTZ1	NM_001363703.2		c.527+209T>A		intron	N/A	NP_001350632.1	G3V4T6
	GSTZ1	NM_145871.3		c.398+209T>A		intron	N/A	NP_665878.2	A0A0A0MR33

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTZ1	ENST00000216465.10	TSL:1 MANE Select	c.524+209T>A		intron	N/A	ENSP00000216465.5	A0A0C4DFM0
	GSTZ1	ENST00000361389.8	TSL:1	c.359+209T>A		intron	N/A	ENSP00000354959.4	O43708-2
	GSTZ1	ENST00000553586.5	TSL:5	c.527+209T>A		intron	N/A	ENSP00000451976.1	G3V4T6

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 2923 AN: 152106 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.00473

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0220

Gnomad ASJ AF: 0.0525

Gnomad EAS AF: 0.0206

Gnomad SAS AF: 0.0567

Gnomad FIN AF: 0.0163

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0231

Gnomad OTH AF: 0.0292

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0192 AC: 2919 AN: 152224 Hom.: 53 Cov.: 32 AF XY: 0.0198 AC XY: 1473 AN XY: 74420

African (AFR) AF: 0.00470 AC: 195 AN: 41530

American (AMR) AF: 0.0219 AC: 335 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0525 AC: 182 AN: 3468

East Asian (EAS) AF: 0.0207 AC: 107 AN: 5176

South Asian (SAS) AF: 0.0563 AC: 272 AN: 4828

European-Finnish (FIN) AF: 0.0163 AC: 173 AN: 10612

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0231 AC: 1569 AN: 67988

Other (OTH) AF: 0.0289 AC: 61 AN: 2112

Alfa AF: 0.0209 Hom.: 6

Bravo AF: 0.0175

Asia WGS AF: 0.0290 AC: 102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.59
DANN	Benign	0.79
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism

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: rs2287397; hg19: chr14-77796911;