6-28510776-ATA-GTT

Variant names:

• chr6-28510776-ATA-GTT
• NM_182701.1:c.214_216delTATinsAAC
• GPX6 p.Tyr72Asn

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_182701.1(GPX6):​c.214_216delTATinsAAC​(p.Tyr72Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y72C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GPX6 NM_182701.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.26
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182701.1. 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
	GPX6	NM_182701.1	MANE Select	c.214_216delTATinsAAC	p.Tyr72Asn	missense	N/A	NP_874360.1	P59796

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPX6	ENST00000361902.5	TSL:1 MANE Select	c.214_216delTATinsAAC	p.Tyr72Asn	missense	N/A	ENSP00000354581.1	P59796
	GPX6	ENST00000474923.1	TSL:1	c.214_216delTATinsAAC	p.Tyr72Asn	missense	N/A	ENSP00000417364.1	A0A182DWH6
	GPX6	ENST00000483058.1	TSL:4	n.433_435delTATinsAAC		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-28478553;