NM_145870.3:c.217-63C>T

Variant names:

• chr14-77327849-C-T
• rs2287396
• NM_145870.3:c.217-63C>T

Variant summary

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

The NM_145870.3(GSTZ1):​c.217-63C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,549,428 control chromosomes in the GnomAD database, including 29,440 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 0.15 (2264 hom., cov: 32)
  • Exomes 𝑓: 0.19 (27176 hom.)
• Consequence: GSTZ1 NM_145870.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.879
• 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.248 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.217-63C>T		intron	N/A	NP_665877.1	A0A0C4DFM0
	GSTZ1	NM_001363703.2		c.220-63C>T		intron	N/A	NP_001350632.1	G3V4T6
	GSTZ1	NM_145871.3		c.216+297C>T		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.217-63C>T		intron	N/A	ENSP00000216465.5	A0A0C4DFM0
	GSTZ1	ENST00000361389.8	TSL:1	c.52-63C>T		intron	N/A	ENSP00000354959.4	O43708-2
	GSTZ1	ENST00000553838.5	TSL:1	n.683C>T		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23453 AN: 151812 Hom.: 2264 Cov.: 32

Gnomad AFR AF: 0.0397

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.192 AC: 267711 AN: 1397498 Hom.: 27176 Cov.: 23 AF XY: 0.192 AC XY: 134183 AN XY: 698008

African (AFR) AF: 0.0312 AC: 1004 AN: 32180

American (AMR) AF: 0.337 AC: 14834 AN: 44072

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 4196 AN: 25222

East Asian (EAS) AF: 0.252 AC: 9922 AN: 39322

South Asian (SAS) AF: 0.230 AC: 19401 AN: 84476

European-Finnish (FIN) AF: 0.161 AC: 8224 AN: 51186

Middle Eastern (MID) AF: 0.202 AC: 1134 AN: 5626

European-Non Finnish (NFE) AF: 0.187 AC: 198176 AN: 1057210

Other (OTH) AF: 0.186 AC: 10820 AN: 58204

GnomAD4 genome AF: 0.154 AC: 23460 AN: 151930 Hom.: 2264 Cov.: 32 AF XY: 0.158 AC XY: 11699 AN XY: 74264

African (AFR) AF: 0.0396 AC: 1640 AN: 41464

American (AMR) AF: 0.252 AC: 3839 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 591 AN: 3470

East Asian (EAS) AF: 0.260 AC: 1335 AN: 5138

South Asian (SAS) AF: 0.227 AC: 1091 AN: 4808

European-Finnish (FIN) AF: 0.169 AC: 1780 AN: 10562

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12556 AN: 67926

Other (OTH) AF: 0.170 AC: 358 AN: 2112

Alfa AF: 0.185 Hom.: 4796

Bravo AF: 0.159

Asia WGS AF: 0.243 AC: 846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.76
PhyloP100		0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs2287396; hg19: chr14-77794192; COSMIC: COSV53622785; COSMIC: COSV53622785;