rs11548

Variant names:

• chr5-151028222-C-A
• rs11548
• NM_002084.5:c.*92C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-151028222-C-A
• chr5-151028222-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002084.5(GPX3):​c.*92C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000101 in 986,012 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: GPX3 NM_002084.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPX3	NM_002084.5	c.*92C>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000388825.9	NP_002075.2
GPX3	NM_001329790.2	c.*92C>A		3_prime_UTR_variant	Exon 6 of 6		NP_001316719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPX3	ENST00000388825.9	c.*92C>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_002084.5	ENSP00000373477.4
GPX3	ENST00000521632.1	c.*58C>A		3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000430743.2
GPX3	ENST00000517973.1	c.*316C>A		downstream_gene_variant		3		ENSP00000429709.1
GPX3	ENST00000520059.1	c.*314C>A		downstream_gene_variant		3		ENSP00000429314.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000101 AC: 1 AN: 986012 Hom.: 0 Cov.: 13 AF XY: 0.00000200 AC XY: 1 AN XY: 498918

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 23878

American (AMR) AF: 0.00 AC: 0 AN: 34286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21058

East Asian (EAS) AF: 0.00 AC: 0 AN: 33958

South Asian (SAS) AF: 0.00 AC: 0 AN: 66976

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45980

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4800

European-Non Finnish (NFE) AF: 0.00000141 AC: 1 AN: 710810

Other (OTH) AF: 0.00 AC: 0 AN: 44266

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.26
DANN	Benign	0.72
PhyloP100		-1.5

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: rs11548; hg19: chr5-150407783;