chr14-77322254-A-G

Variant names:

• chr14-77322254-A-G
• rs2111699
• NM_145870.3:c.15+1071A>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.15+1071A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,074 control chromosomes in the GnomAD database, including 7,665 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 0.31 (7665 hom., cov: 32)
• Consequence: GSTZ1 NM_145870.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.479
• Publications: 10 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.431 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.15+1071A>G		intron	N/A	NP_665877.1	A0A0C4DFM0
	GSTZ1	NM_145871.3		c.15+1071A>G		intron	N/A	NP_665878.2	A0A0A0MR33
	GSTZ1	NM_001312660.2		c.-336-293A>G		intron	N/A	NP_001299589.1	O43708-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTZ1	ENST00000216465.10	TSL:1 MANE Select	c.15+1071A>G		intron	N/A	ENSP00000216465.5	A0A0C4DFM0
	GSTZ1	ENST00000361389.8	TSL:1	c.-336-293A>G		intron	N/A	ENSP00000354959.4	O43708-2
	GSTZ1	ENST00000553838.5	TSL:1	n.185+1071A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47873 AN: 151958 Hom.: 7657 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.315 AC: 47889 AN: 152074 Hom.: 7665 Cov.: 32 AF XY: 0.313 AC XY: 23271 AN XY: 74348

African (AFR) AF: 0.310 AC: 12840 AN: 41486

American (AMR) AF: 0.248 AC: 3792 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1030 AN: 3470

East Asian (EAS) AF: 0.446 AC: 2314 AN: 5184

South Asian (SAS) AF: 0.200 AC: 962 AN: 4822

European-Finnish (FIN) AF: 0.388 AC: 4095 AN: 10556

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.322 AC: 21894 AN: 67968

Other (OTH) AF: 0.292 AC: 615 AN: 2104

Alfa AF: 0.309 Hom.: 3863

Bravo AF: 0.306

Asia WGS AF: 0.287 AC: 996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	10
DANN	Benign	0.79
PhyloP100		0.48
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: rs2111699; hg19: chr14-77788597;