rs372803804

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001352302.2(TXNRD2):​c.-90G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,412,008 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 27)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TXNRD2
NM_001352302.2 5_prime_UTR_premature_start_codon_gain

Scores

2
7
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.56
Variant links:
Genes affected
TXNRD2 (HGNC:18155): (thioredoxin reductase 2) The protein encoded by this gene belongs to the pyridine nucleotide-disulfide oxidoreductase family, and is a member of the thioredoxin (Trx) system. Three thioredoxin reductase (TrxR) isozymes are found in mammals. TrxRs are selenocysteine-containing flavoenzymes, which reduce thioredoxins, as well as other substrates, and play a key role in redox homoeostasis. This gene encodes a mitochondrial form important for scavenging reactive oxygen species in mitochondria. It functions as a homodimer containing FAD, and selenocysteine (Sec) at the active site. Sec is encoded by UGA codon that normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, the Sec insertion sequence (SECIS) element, which is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. Alternatively spliced transcript variants encoding different isoforms, including a few localized in the cytosol and some lacking the C-terminal Sec residue, have been found for this gene. [provided by RefSeq, Jun 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TXNRD2NM_006440.5 linkc.199G>T p.Val67Leu missense_variant Exon 3 of 18 ENST00000400521.7 NP_006431.2 Q9NNW7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TXNRD2ENST00000400521.7 linkc.199G>T p.Val67Leu missense_variant Exon 3 of 18 1 NM_006440.5 ENSP00000383365.1 Q9NNW7-1

Frequencies

GnomAD3 genomes
Cov.:
27
GnomAD4 exome
AF:
0.00000142
AC:
2
AN:
1412008
Hom.:
0
Cov.:
30
AF XY:
0.00000143
AC XY:
1
AN XY:
698002
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.20e-7
Gnomad4 OTH exome
AF:
0.0000171
GnomAD4 genome
Cov.:
27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
0.065
T
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.13
.;.;.;T;T;.
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
0.98
.;.;.;D;D;D
M_CAP
Benign
0.020
T
MetaRNN
Uncertain
0.47
T;T;T;T;T;T
MetaSVM
Benign
-0.81
T
MutationAssessor
Benign
0.47
.;.;.;N;.;.
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-2.5
N;N;N;N;.;N
REVEL
Benign
0.27
Sift
Benign
0.41
T;T;T;T;.;T
Sift4G
Benign
0.64
T;T;T;T;T;T
Polyphen
0.98, 0.98
.;.;.;D;.;D
Vest4
0.41
MutPred
0.54
.;.;.;Gain of sheet (P = 0.0827);.;Gain of sheet (P = 0.0827);
MVP
0.69
MPC
0.31
ClinPred
0.96
D
GERP RS
4.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-19907096; API