6-28510118-T-C

Variant names:

• chr6-28510118-T-C
• rs4713167
• NM_182701.1:c.241+633A>G

Variant summary

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

The NM_182701.1(GPX6):​c.241+633A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,088 control chromosomes in the GnomAD database, including 14,405 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 0.41 (14405 hom., cov: 33)
• Consequence: GPX6 NM_182701.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.889

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 (AFR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPX6	NM_182701.1	c.241+633A>G		intron_variant	Intron 2 of 4	ENST00000361902.5	NP_874360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPX6	ENST00000361902.5	c.241+633A>G		intron_variant	Intron 2 of 4	1	NM_182701.1	ENSP00000354581.1
GPX6	ENST00000474923.1	c.241+633A>G		intron_variant	Intron 2 of 3	1		ENSP00000417364.1
GPX6	ENST00000483058.1	n.460+633A>G		intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62657 AN: 151970 Hom.: 14359 Cov.: 33

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.413 AC: 62765 AN: 152088 Hom.: 14405 Cov.: 33 AF XY: 0.410 AC XY: 30458 AN XY: 74312

Gnomad4 AFR AF: 0.620

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.517

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.401

Alfa AF: 0.365 Hom.: 1912

Bravo AF: 0.431

Asia WGS AF: 0.404 AC: 1402 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	0.51
DANN	Benign	0.46

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: rs4713167; hg19: chr6-28477895;