rs8177569

Variant names:

• chr14-77329325-A-C
• rs8177569
• NM_145870.3:c.421+124A>C

Your query was ambiguous. Multiple possible variants found:

• chr14-77329325-A-C
• chr14-77329325-A-G
• chr14-77329325-A-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.421+124A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0417 in 731,860 control chromosomes in the GnomAD database, including 841 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 0.055 (285 hom., cov: 33)
  • Exomes 𝑓: 0.038 (556 hom.)
• Consequence: GSTZ1 NM_145870.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.625
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.097 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.421+124A>C		intron	N/A	NP_665877.1	A0A0C4DFM0
	GSTZ1	NM_001363703.2		c.424+124A>C		intron	N/A	NP_001350632.1	G3V4T6
	GSTZ1	NM_145871.3		c.295+124A>C		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.421+124A>C		intron	N/A	ENSP00000216465.5	A0A0C4DFM0
	GSTZ1	ENST00000361389.8	TSL:1	c.256+124A>C		intron	N/A	ENSP00000354959.4	O43708-2
	GSTZ1	ENST00000553586.5	TSL:5	c.424+124A>C		intron	N/A	ENSP00000451976.1	G3V4T6

Frequencies

GnomAD3 genomes AF: 0.0545 AC: 8290 AN: 152142 Hom.: 287 Cov.: 33

Gnomad AFR AF: 0.0995

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0350

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0258

Gnomad FIN AF: 0.0516

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0378

Gnomad OTH AF: 0.0559

GnomAD4 exome AF: 0.0383 AC: 22193 AN: 579600 Hom.: 556 Cov.: 6 AF XY: 0.0378 AC XY: 11702 AN XY: 309908

African (AFR) AF: 0.104 AC: 1698 AN: 16332

American (AMR) AF: 0.0242 AC: 828 AN: 34266

Ashkenazi Jewish (ASJ) AF: 0.0512 AC: 971 AN: 18980

East Asian (EAS) AF: 0.000183 AC: 6 AN: 32732

South Asian (SAS) AF: 0.0283 AC: 1766 AN: 62378

European-Finnish (FIN) AF: 0.0495 AC: 2219 AN: 44798

Middle Eastern (MID) AF: 0.0517 AC: 125 AN: 2420

European-Non Finnish (NFE) AF: 0.0395 AC: 13302 AN: 336924

Other (OTH) AF: 0.0415 AC: 1278 AN: 30770

GnomAD4 genome AF: 0.0545 AC: 8301 AN: 152260 Hom.: 285 Cov.: 33 AF XY: 0.0537 AC XY: 3997 AN XY: 74472

African (AFR) AF: 0.0995 AC: 4133 AN: 41544

American (AMR) AF: 0.0350 AC: 535 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0550 AC: 191 AN: 3472

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5170

South Asian (SAS) AF: 0.0259 AC: 125 AN: 4832

European-Finnish (FIN) AF: 0.0516 AC: 548 AN: 10616

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0378 AC: 2569 AN: 68010

Other (OTH) AF: 0.0553 AC: 117 AN: 2114

Alfa AF: 0.0436 Hom.: 194

Bravo AF: 0.0555

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.73
PhyloP100		0.63
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)		0.0		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: rs8177569; hg19: chr14-77795668;