chr22-36476826-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_012473.4(TXN2):​c.294G>A​(p.Pro98=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00742 in 1,614,164 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 7 hom., cov: 32)
Exomes 𝑓: 0.0076 ( 61 hom. )

Consequence

TXN2
NM_012473.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.65
Variant links:
Genes affected
TXN2 (HGNC:17772): (thioredoxin 2) This nuclear gene encodes a mitochondrial member of the thioredoxin family, a group of small multifunctional redox-active proteins. The encoded protein may play important roles in the regulation of the mitochondrial membrane potential and in protection against oxidant-induced apoptosis. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 22-36476826-C-T is Benign according to our data. Variant chr22-36476826-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 774540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.65 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TXN2NM_012473.4 linkuse as main transcriptc.294G>A p.Pro98= synonymous_variant 3/4 ENST00000216185.7
TXN2XM_006724226.2 linkuse as main transcriptc.294G>A p.Pro98= synonymous_variant 3/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TXN2ENST00000216185.7 linkuse as main transcriptc.294G>A p.Pro98= synonymous_variant 3/41 NM_012473.4 P1

Frequencies

GnomAD3 genomes
AF:
0.00586
AC:
892
AN:
152158
Hom.:
7
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00162
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00668
Gnomad ASJ
AF:
0.0141
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00394
Gnomad FIN
AF:
0.00226
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.00901
Gnomad OTH
AF:
0.00670
GnomAD3 exomes
AF:
0.00635
AC:
1597
AN:
251486
Hom.:
9
AF XY:
0.00645
AC XY:
877
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.00105
Gnomad AMR exome
AF:
0.00593
Gnomad ASJ exome
AF:
0.0147
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00323
Gnomad FIN exome
AF:
0.00273
Gnomad NFE exome
AF:
0.00877
Gnomad OTH exome
AF:
0.0116
GnomAD4 exome
AF:
0.00758
AC:
11088
AN:
1461888
Hom.:
61
Cov.:
33
AF XY:
0.00754
AC XY:
5486
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00111
Gnomad4 AMR exome
AF:
0.00595
Gnomad4 ASJ exome
AF:
0.0156
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00342
Gnomad4 FIN exome
AF:
0.00333
Gnomad4 NFE exome
AF:
0.00839
Gnomad4 OTH exome
AF:
0.00780
GnomAD4 genome
AF:
0.00585
AC:
891
AN:
152276
Hom.:
7
Cov.:
32
AF XY:
0.00561
AC XY:
418
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.00161
Gnomad4 AMR
AF:
0.00667
Gnomad4 ASJ
AF:
0.0141
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00395
Gnomad4 FIN
AF:
0.00226
Gnomad4 NFE
AF:
0.00901
Gnomad4 OTH
AF:
0.00663
Alfa
AF:
0.00786
Hom.:
4
Bravo
AF:
0.00567
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.00845
EpiControl
AF:
0.00836

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2024TXN2: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 29, 2024- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Combined oxidative phosphorylation deficiency 29 Benign:1
Likely benign, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsOct 05, 2021- -
TXN2-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJan 13, 2020This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.68
CADD
Benign
3.0
DANN
Benign
0.56
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

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

Other links and lift over

dbSNP: rs150502647; hg19: chr22-36872873; API