Genetic Variant NM_006541.5:c.53C>A (chr10-130136473-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006541.5(GLRX3):c.53C>A(p.Ser18*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GLRX3
NM_006541.5 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.04

Publications

0 publications found

Variant links:

Genes affected

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]

GLRX3 links:

ENSG00000300559 (HGNC:):

ENSG00000300559 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006541.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLRX3	NM_006541.5	MANE Select	c.53C>A	p.Ser18*	stop_gained	Exon 1 of 11	NP_006532.2	A0A140VJK1
GLRX3	NM_001199868.2		c.53C>A	p.Ser18*	stop_gained	Exon 1 of 12	NP_001186797.1	O76003
GLRX3	NM_001321980.2		c.-475C>A		5_prime_UTR	Exon 1 of 12	NP_001308909.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLRX3	ENST00000331244.10	TSL:1 MANE Select	c.53C>A	p.Ser18*	stop_gained	Exon 1 of 11	ENSP00000330836.5	O76003
GLRX3	ENST00000481034.1	TSL:1	n.53C>A		non_coding_transcript_exon	Exon 1 of 13	ENSP00000435445.1	O76003
GLRX3	ENST00000861475.1		c.53C>A	p.Ser18*	stop_gained	Exon 1 of 12	ENSP00000531534.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

19152

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1113824

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

529958

African (AFR)

AF:

0.00

AC:

AN:

23252

American (AMR)

AF:

0.00

AC:

AN:

9466

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14810

East Asian (EAS)

AF:

0.00

AC:

AN:

26844

South Asian (SAS)

AF:

0.00

AC:

AN:

24052

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36074

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2986

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

931818

Other (OTH)

AF:

0.00

AC:

AN:

44522

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.44

BayesDel_noAF

Pathogenic

0.40

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Uncertain

0.29

Eigen_PC

Benign

0.028

FATHMM_MKL

Benign

0.0023

PhyloP100

1.0

Vest4

0.065

GERP RS

3.9

PromoterAI

0.019

Neutral

(source)

Mutation Taster

=6/194

disease causing (fs/PTC)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over