rs2859358

Positions:

• chr6-28505044-T-A
• chr6-28505044-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182701.1(GPX6):​c.460-546A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,176 control chromosomes in the GnomAD database, including 7,699 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 0.29 (7699 hom., cov: 32)
• Consequence: GPX6 NM_182701.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280

Genes affected

GPX6 (HGNC:4558): (glutathione peroxidase 6) The protein encoded by this gene belongs to the glutathione peroxidase family, members of which catalyze the reduction of hydrogen peroxide, organic hydroperoxides and lipid hydroperoxides, and thereby protect cells against oxidative damage. Several isozymes of this gene family exist in vertebrates, which vary in cellular location and substrate specificity. Expression of this gene has been observed in embryos and olfactory epithelium; however, the exact function of this gene is not known. This isozyme is a selenoprotein in humans, containing the rare amino acid selenocysteine (Sec) at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. The orthologs of this gene in mouse and rat (and some other species) contain a cysteine (Cys) residue in place of the Sec residue, and their corresponding mRNAs lack SECIS element. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPX6	NM_182701.1	c.460-546A>T		intron_variant		ENST00000361902.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPX6	ENST00000361902.5	c.460-546A>T		intron_variant		1	NM_182701.1	P1
GPX6	ENST00000474923.1	c.360-546A>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43648 AN: 152058 Hom.: 7668 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.287 AC: 43730 AN: 152176 Hom.: 7699 Cov.: 32 AF XY: 0.290 AC XY: 21550 AN XY: 74416

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.269

Alfa AF: 0.228 Hom.: 649

Bravo AF: 0.306

Asia WGS AF: 0.378 AC: 1314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs2859358; hg19: chr6-28472821;