NM_015696.5:c.445G>A

Variant names:

• chr1-52608306-G-A
• NM_015696.5:c.445G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015696.5(GPX7):​c.445G>A​(p.Val149Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPX7 NM_015696.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.51
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12505758).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015696.5. 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
	GPX7	NM_015696.5	MANE Select	c.445G>A	p.Val149Ile	missense	Exon 3 of 3	NP_056511.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPX7	ENST00000361314.5	TSL:1 MANE Select	c.445G>A	p.Val149Ile	missense	Exon 3 of 3	ENSP00000354677.4	Q96SL4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.85	L
PhyloP100		3.5
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.056
Sift	Benign	0.19	T
Sift4G	Benign	0.32	T
Polyphen		0.19	B
Vest4		0.085
MutPred		0.53		Loss of ubiquitination at K146 (P = 0.0834)
MVP		0.13
MPC		0.18
ClinPred		0.60	D
GERP RS		3.6
Varity_R		0.074
gMVP		0.35
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr1-53073978;