Variant chr22-19876812-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000400519.6(TXNRD2):c.*293C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 313,650 control chromosomes in the GnomAD database, including 2,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1156 hom., cov: 33)

Exomes 𝑓: 0.12 ( 1550 hom. )

Consequence

TXNRD2
ENST00000400519.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.370

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]

TXNRD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 22-19876812-G-A is Benign according to our data. Variant chr22-19876812-G-A is described in ClinVar as [Benign]. Clinvar id is 1298115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNRD2	NM_006440.5 linkuse as main transcript	c.*65+228C>T		intron_variant		ENST00000400521.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNRD2	ENST00000400521.7 linkuse as main transcript	c.*65+228C>T		intron_variant		1	NM_006440.5	P4	Q9NNW7-1

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

17011

AN:

152094

Hom.:

1152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0551

Gnomad AMI

AF:

0.153

Gnomad AMR

AF:

0.107

Gnomad ASJ

AF:

0.202

Gnomad EAS

AF:

0.0100

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.0921

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.153

Gnomad OTH

AF:

0.119

GnomAD4 exome

AF:

0.124

AC:

20012

AN:

161438

Hom.:

1550

Cov.:

AF XY:

0.125

AC XY:

10260

AN XY:

81766

show subpopulations

Gnomad4 AFR exome

AF:

0.0508

Gnomad4 AMR exome

AF:

0.0886

Gnomad4 ASJ exome

AF:

0.198

Gnomad4 EAS exome

AF:

0.00579

Gnomad4 SAS exome

AF:

0.0911

Gnomad4 FIN exome

AF:

0.0898

Gnomad4 NFE exome

AF:

0.148

Gnomad4 OTH exome

AF:

0.123

GnomAD4 genome

AF:

0.112

AC:

17040

AN:

152212

Hom.:

1156

Cov.:

AF XY:

0.109

AC XY:

8137

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0554

Gnomad4 AMR

AF:

0.107

Gnomad4 ASJ

AF:

0.202

Gnomad4 EAS

AF:

0.0100

Gnomad4 SAS

AF:

0.103

Gnomad4 FIN

AF:

0.0921

Gnomad4 NFE

AF:

0.154

Gnomad4 OTH

AF:

0.120

Alfa

AF:

0.130

Hom.:

182

Bravo

AF:

0.108

Asia WGS

AF:

0.0670

AC:

232

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.0

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over