chr14-77326898-G-T

Position:

• chr14-77326898-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_145870.3(GSTZ1):​c.128G>T​(p.Gly43Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSTZ1 NM_145870.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.48

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTZ1	NM_145870.3	c.128G>T	p.Gly43Val	missense_variant	3/9	ENST00000216465.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTZ1	ENST00000216465.10	c.128G>T	p.Gly43Val	missense_variant	3/9	1	NM_145870.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1447860 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 719332

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2021

The c.128G>T (p.G43V) alteration is located in exon 3 (coding exon 3) of the GSTZ1 gene. This alteration results from a G to T substitution at nucleotide position 128, causing the glycine (G) at amino acid position 43 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;T;T;.;.
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	1.0	D;D;D;D;D
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.66	D;D;D;D;D
MetaSVM	Benign	-0.72	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-7.6	D;D;D;D;D
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D
Vest4		0.61
MutPred		0.53		Loss of disorder (P = 0.0429);Loss of disorder (P = 0.0429);Loss of disorder (P = 0.0429);Loss of disorder (P = 0.0429);.;
MVP		0.51
MPC		0.36
ClinPred		1.0	D
GERP RS		5.6
gMVP		0.90

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-77793241;