NM_145870.3:c.16-341T>A

Variant names:

• chr14-77324529-T-A
• rs8016187
• NM_145870.3:c.16-341T>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.16-341T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,387,252 control chromosomes in the GnomAD database, including 59,162 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 0.24 (5183 hom., cov: 32)
  • Exomes 𝑓: 0.29 (53979 hom.)
• Consequence: GSTZ1 NM_145870.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890
• Publications: 8 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 (EAS) allele frequency at 95% confidence interval = 0.423 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTZ1	NM_145870.3	MANE Select	c.16-341T>A		intron	N/A	NP_665877.1
	GSTZ1	NM_145871.3		c.16-341T>A		intron	N/A	NP_665878.2
	GSTZ1	NM_001312660.2		c.-150-341T>A		intron	N/A	NP_001299589.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTZ1	ENST00000216465.10	TSL:1 MANE Select	c.16-341T>A		intron	N/A	ENSP00000216465.5
	GSTZ1	ENST00000361389.8	TSL:1	c.-150-341T>A		intron	N/A	ENSP00000354959.4
	GSTZ1	ENST00000553838.5	TSL:1	n.186-341T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35938 AN: 151952 Hom.: 5172 Cov.: 32

Gnomad AFR AF: 0.0831

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.288 AC: 355542 AN: 1235184 Hom.: 53979 Cov.: 18 AF XY: 0.285 AC XY: 175720 AN XY: 616836

African (AFR) AF: 0.0769 AC: 2211 AN: 28770

American (AMR) AF: 0.178 AC: 6328 AN: 35520

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 6735 AN: 24344

East Asian (EAS) AF: 0.455 AC: 15939 AN: 35062

South Asian (SAS) AF: 0.175 AC: 13316 AN: 76238

European-Finnish (FIN) AF: 0.388 AC: 13101 AN: 33784

Middle Eastern (MID) AF: 0.173 AC: 935 AN: 5396

European-Non Finnish (NFE) AF: 0.300 AC: 282480 AN: 943048

Other (OTH) AF: 0.273 AC: 14497 AN: 53022

GnomAD4 genome AF: 0.236 AC: 35955 AN: 152068 Hom.: 5183 Cov.: 32 AF XY: 0.239 AC XY: 17733 AN XY: 74310

African (AFR) AF: 0.0831 AC: 3450 AN: 41526

American (AMR) AF: 0.190 AC: 2909 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 974 AN: 3470

East Asian (EAS) AF: 0.438 AC: 2258 AN: 5154

South Asian (SAS) AF: 0.190 AC: 919 AN: 4828

European-Finnish (FIN) AF: 0.393 AC: 4139 AN: 10538

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20503 AN: 67952

Other (OTH) AF: 0.227 AC: 480 AN: 2112

Alfa AF: 0.279 Hom.: 828

Bravo AF: 0.217

Asia WGS AF: 0.308 AC: 1066 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	10
DANN	Benign	0.70
PhyloP100		0.089
PromoterAI		-0.042	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8016187; hg19: chr14-77790872; COSMIC: COSV53623088; COSMIC: COSV53623088;