chr1-52606873-G-A

Position:

• chr1-52606873-G-A

Variant summary

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

The NM_015696.5(GPX7):​c.328G>A​(p.Val110Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: GPX7 NM_015696.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.51

Genes affected

GPX7 (HGNC:4559): (glutathione peroxidase 7) Enables catalase activity. Predicted to be involved in cellular response to oxidative stress. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

GPX7 (HGNC:):

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	Protein	UniProt
GPX7	NM_015696.5	c.328G>A	p.Val110Ile	missense_variant	2/3	ENST00000361314.5	NP_056511.2
GPX7	XM_047418560.1	c.220G>A	p.Val74Ile	missense_variant	2/3		XP_047274516.1
GPX7	XM_047418564.1	c.199G>A	p.Val67Ile	missense_variant	2/3		XP_047274520.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPX7	ENST00000361314.5	c.328G>A	p.Val110Ile	missense_variant	2/3	1	NM_015696.5	ENSP00000354677.4
GPX7	ENST00000459779.1	n.338G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000752 AC: 11 AN: 1461892 Hom.: 0 Cov.: 35 AF XY: 0.00000550 AC XY: 4 AN XY: 727248

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: 0.00000899

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

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

Dec 08, 2023

The c.328G>A (p.V110I) alteration is located in exon 2 (coding exon 2) of the GPX7 gene. This alteration results from a G to A substitution at nucleotide position 328, causing the valine (V) at amino acid position 110 to be replaced by an isoleucine (I). 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	Benign	0.14
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.094	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.25
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.010	D
Polyphen		0.94	P
Vest4		0.35
MutPred		0.71		Loss of catalytic residue at V110 (P = 0.02);
MVP		0.45
MPC		0.56
ClinPred		0.93	D
GERP RS		5.2
Varity_R		0.19
gMVP		0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs747412028; hg19: chr1-53072545;