GeneBe

rs4077561

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001093771.3(TXNRD1):​c.305-2341T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 29)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

TXNRD1
NM_001093771.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.03

Publications

8 publications found
Variant links:
Genes affected
TXNRD1 (HGNC:12437): (thioredoxin reductase 1) 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 an ubiquitously expressed, cytosolic form of TrxR, which 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. Alternative splicing, primarily at the 5' end, results in transcript variants encoding same or different isoforms, including a glutaredoxin-containing isoform that is predominantly expressed in testis. [provided by RefSeq, May 2017]

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ACMG classification

Classification was made for transcript

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=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001093771.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TXNRD1
NM_001093771.3
MANE Select
c.305-2341T>A
intron
N/ANP_001087240.1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TXNRD1
ENST00000525566.6
TSL:1 MANE Select
c.305-2341T>A
intron
N/AENSP00000434516.1
TXNRD1
ENST00000526266.5
TSL:4
c.-209+430T>A
intron
N/AENSP00000431294.1
TXNRD1
ENST00000503506.6
TSL:1
c.-666T>A
upstream_gene
N/AENSP00000421934.2

Frequencies

GnomAD3 genomes
Cov.:
29
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
209324
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
99038
African (AFR)
AF:
0.00
AC:
0
AN:
3998
American (AMR)
AF:
0.00
AC:
0
AN:
230
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
1262
East Asian (EAS)
AF:
0.00
AC:
0
AN:
860
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4188
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
76
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
382
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
191718
Other (OTH)
AF:
0.00
AC:
0
AN:
6610
GnomAD4 genome
Cov.:
29
Alfa
AF:
0.00
Hom.:
34581

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.45
DANN
Benign
0.40
PhyloP100
-2.0
PromoterAI
0.015
Neutral

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

Other links and lift over

dbSNP: rs4077561; hg19: chr12-104680368; API