rs8177441

Variant names:

• chr5-151026433-G-C
• rs8177441
• NM_002084.5:c.242-467G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002084.5(GPX3):​c.242-467G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 154,074 control chromosomes in the GnomAD database, including 4,066 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 0.22 (4009 hom., cov: 32)
  • Exomes 𝑓: 0.21 (57 hom.)
• Consequence: GPX3 NM_002084.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.964
• Publications: 5 publications found

Genes affected

GPX3 (HGNC:4555): (glutathione peroxidase 3) The protein encoded by this gene belongs to the glutathione peroxidase family, members of which catalyze the reduction of organic hydroperoxides and hydrogen peroxide (H2O2) by glutathione, and thereby protect cells against oxidative damage. Several isozymes of this gene family exist in vertebrates, which vary in cellular location and substrate specificity. This isozyme is secreted, and is abundantly found in plasma. Downregulation of expression of this gene by promoter hypermethylation has been observed in a wide spectrum of human malignancies, including thyroid cancer, hepatocellular carcinoma and chronic myeloid leukemia. This isozyme is also a selenoprotein, 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. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002084.5. 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
	GPX3	NM_002084.5	MANE Select	c.242-467G>C		intron	N/A	NP_002075.2
	GPX3	NM_001329790.2		c.269-467G>C		intron	N/A	NP_001316719.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPX3	ENST00000388825.9	TSL:1 MANE Select	c.242-467G>C		intron	N/A	ENSP00000373477.4	P22352
	GPX3	ENST00000521632.1	TSL:5	c.149-467G>C		intron	N/A	ENSP00000430743.2	H0YC19
	GPX3	ENST00000521650.5	TSL:2	c.269-467G>C		intron	N/A	ENSP00000427873.1	E5RG32

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33008 AN: 151908 Hom.: 4008 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.227

GnomAD4 exome AF: 0.209 AC: 428 AN: 2044 Hom.: 57 Cov.: 0 AF XY: 0.206 AC XY: 242 AN XY: 1172

African (AFR) AF: 0.125 AC: 7 AN: 56

American (AMR) AF: 0.238 AC: 20 AN: 84

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 19 AN: 74

East Asian (EAS) AF: 0.577 AC: 30 AN: 52

South Asian (SAS) AF: 0.205 AC: 9 AN: 44

European-Finnish (FIN) AF: 0.150 AC: 12 AN: 80

Middle Eastern (MID) AF: 0.300 AC: 3 AN: 10

European-Non Finnish (NFE) AF: 0.197 AC: 300 AN: 1522

Other (OTH) AF: 0.230 AC: 28 AN: 122

GnomAD4 genome AF: 0.217 AC: 33012 AN: 152030 Hom.: 4009 Cov.: 32 AF XY: 0.221 AC XY: 16394 AN XY: 74310

African (AFR) AF: 0.195 AC: 8107 AN: 41476

American (AMR) AF: 0.229 AC: 3492 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 814 AN: 3468

East Asian (EAS) AF: 0.576 AC: 2962 AN: 5138

South Asian (SAS) AF: 0.339 AC: 1634 AN: 4816

European-Finnish (FIN) AF: 0.196 AC: 2079 AN: 10588

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12998 AN: 67968

Other (OTH) AF: 0.224 AC: 471 AN: 2106

Alfa AF: 0.207 Hom.: 404

Bravo AF: 0.221

Asia WGS AF: 0.383 AC: 1332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.4
DANN	Benign	0.73
PhyloP100		0.96
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8177441; hg19: chr5-150405994;