NM_145870.3:c.94G>T

Variant names:

• chr14-77326864-G-T
• rs7975
• NM_145870.3:c.94G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_145870.3(GSTZ1):​c.94G>T​(p.Glu32*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GSTZ1 NM_145870.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.23
• Publications: 72 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.94G>T	p.Glu32*	stop_gained	Exon 3 of 9	NP_665877.1	A0A0C4DFM0
	GSTZ1	NM_001363703.2		c.97G>T	p.Glu33*	stop_gained	Exon 3 of 9	NP_001350632.1	G3V4T6
	GSTZ1	NM_145871.3		c.94G>T	p.Glu32*	stop_gained	Exon 3 of 8	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.94G>T	p.Glu32*	stop_gained	Exon 3 of 9	ENSP00000216465.5	A0A0C4DFM0
	GSTZ1	ENST00000361389.8	TSL:1	c.-72G>T		5_prime_UTR	Exon 4 of 10	ENSP00000354959.4	O43708-2
	GSTZ1	ENST00000553838.5	TSL:1	n.264G>T		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000945 Hom.: 23811

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.55
CADD	Pathogenic	41
DANN	Uncertain	1.0
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.92
FATHMM_MKL	Uncertain	0.93	D
PhyloP100		5.2
Vest4		0.72
GERP RS		5.6
Mutation Taster		=6/194	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs7975; hg19: chr14-77793207;