rs2281843

Positions:

• chr10-130181652-T-C

Variant summary

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

The XM_047426136.1(LOC124902561):​c.-6201+1331T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 152,232 control chromosomes in the GnomAD database, including 535 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 0.057 (535 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LOC124902561 XM_047426136.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473

Genes affected

LOC124902561 (HGNC:):

GLRX3 (HGNC:15987): (glutaredoxin 3) This gene encodes a member of the glutaredoxin family. Glutaredoxins are oxidoreductase enzymes that reduce a variety of substrates using glutathione as a cofactor. The encoded protein binds to and modulates the function of protein kinase C theta. The encoded protein may also inhibit apoptosis and play a role in cellular growth, and the expression of this gene may be a marker for cancer. Pseudogenes of this gene are located on the short arm of chromosomes 6 and 9. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124902561	XM_047426136.1	c.-6201+1331T>C		intron_variant			XP_047282092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLRX3	ENST00000481034.1	c.*237+1331T>C		intron_variant, NMD_transcript_variant		1		ENSP00000435445
GLRX3	ENST00000368644.5	c.*1568T>C		3_prime_UTR_variant	12/12	2		ENSP00000357633	P1
GLRX3	ENST00000619341.1	n.137+1331T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0566 AC: 8614 AN: 152114 Hom.: 533 Cov.: 33

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0625

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.0475

Gnomad FIN AF: 0.0206

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00716

Gnomad OTH AF: 0.0531

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0567 AC: 8634 AN: 152232 Hom.: 535 Cov.: 33 AF XY: 0.0565 AC XY: 4202 AN XY: 74434

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.0625

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.100

Gnomad4 SAS AF: 0.0473

Gnomad4 FIN AF: 0.0206

Gnomad4 NFE AF: 0.00716

Gnomad4 OTH AF: 0.0525

Alfa AF: 0.0355 Hom.: 37

Bravo AF: 0.0653

Asia WGS AF: 0.0700 AC: 245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.4
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2281843; hg19: chr10-131979916;