1-193104436-T-A

Variant names:

• chr1-193104436-T-A
• rs10801174
• NM_197962.3:c.119+828A>T

Variant summary

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

The NM_197962.3(GLRX2):​c.119+828A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 152,064 control chromosomes in the GnomAD database, including 29,035 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 0.61 (29035 hom., cov: 32)
• Consequence: GLRX2 NM_197962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142
• Publications: 7 publications found

Genes affected

GLRX2 (HGNC:16065): (glutaredoxin 2) The protein encoded by this gene is a member of the glutaredoxin family of proteins, which maintain cellular thiol homeostasis. These proteins are thiol-disulfide oxidoreductases that use a glutathione-binding site and one or two active cysteines in their active site. This gene undergoes alternative splicing to produce multiple isoforms, one of which is ubiquitously expressed and localizes to mitochondria, where it functions in mitochondrial redox homeostasis and is important for the protection against and recovery from oxidative stress. Other isoforms, which have more restrictive expression patterns, show cytosolic and nuclear localization, and are thought to function in cellular differentiation and transformation, possibly with a role in tumor progression. [provided by RefSeq, Aug 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRX2	NM_197962.3	c.119+828A>T		intron_variant	Intron 1 of 3	ENST00000367439.8	NP_932066.1
GLRX2	NM_016066.4	c.122+1081A>T		intron_variant	Intron 1 of 3		NP_057150.2
GLRX2	NM_001243399.2	c.-2+1182A>T		intron_variant	Intron 1 of 3		NP_001230328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRX2	ENST00000367439.8	c.119+828A>T		intron_variant	Intron 1 of 3	1	NM_197962.3	ENSP00000356409.3
GLRX2	ENST00000367440.3	c.122+1081A>T		intron_variant	Intron 1 of 3	1		ENSP00000356410.3
GLRX2	ENST00000472197.1	n.440+1182A>T		intron_variant	Intron 1 of 3	5
GLRX2	ENST00000608166.2	n.119+828A>T		intron_variant	Intron 1 of 4	6		ENSP00000494652.1

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92732 AN: 151946 Hom.: 29018 Cov.: 32

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.610 AC: 92791 AN: 152064 Hom.: 29035 Cov.: 32 AF XY: 0.613 AC XY: 45537 AN XY: 74324

African (AFR) AF: 0.474 AC: 19667 AN: 41452

American (AMR) AF: 0.665 AC: 10167 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2357 AN: 3468

East Asian (EAS) AF: 0.449 AC: 2321 AN: 5170

South Asian (SAS) AF: 0.767 AC: 3700 AN: 4826

European-Finnish (FIN) AF: 0.612 AC: 6466 AN: 10558

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45870 AN: 67982

Other (OTH) AF: 0.646 AC: 1362 AN: 2108

Alfa AF: 0.523 Hom.: 1646

Bravo AF: 0.602

Asia WGS AF: 0.640 AC: 2225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.9
DANN	Benign	0.52
PhyloP100		0.14
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: rs10801174; hg19: chr1-193073566;