dbSNP rs4135192: TXN:c.129+50T>C (chr9-110251308-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003329.4(TXN):c.129+50T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,374,862 control chromosomes in the GnomAD database, including 58,931 homozygotes. 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: 𝑓 0.21 ( 4350 hom., cov: 29)

Exomes 𝑓: 0.29 ( 54581 hom. )

Consequence

TXN
NM_003329.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.646

Publications

13 publications found

Variant links:

Genes affected

TXN (HGNC:12435): (thioredoxin) The protein encoded by this gene acts as a homodimer and is involved in many redox reactions. The encoded protein is active in the reversible S-nitrosylation of cysteines in certain proteins, which is part of the response to intracellular nitric oxide. This protein is found in the cytoplasm. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

TXN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXN	NM_003329.4 link	c.129+50T>C		intron_variant	Intron 2 of 4	ENST00000374517.6	NP_003320.2	P10599-1H9ZYJ2
TXN	NM_001244938.2 link	c.129+50T>C		intron_variant	Intron 2 of 3		NP_001231867.1	P10599-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXN	ENST00000374517.6 link	c.129+50T>C		intron_variant	Intron 2 of 4	1	NM_003329.4	ENSP00000363641.5		P10599-1
TXN	ENST00000374515.9 link	c.129+50T>C		intron_variant	Intron 2 of 3	1		ENSP00000363639.5		P10599-2

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32296

AN:

151630

Hom.:

4348

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0638

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.172

Gnomad ASJ

AF:

0.182

Gnomad EAS

AF:

0.0865

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.267

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.316

Gnomad OTH

AF:

0.195

GnomAD2 exomes

AF:

0.235

AC:

57490

AN:

244654

AF XY:

0.245

show subpopulations

Gnomad AFR exome

AF:

0.0591

Gnomad AMR exome

AF:

0.118

Gnomad ASJ exome

AF:

0.197

Gnomad EAS exome

AF:

0.0825

Gnomad FIN exome

AF:

0.266

Gnomad NFE exome

AF:

0.316

Gnomad OTH exome

AF:

0.239

GnomAD4 exome

AF:

0.288

AC:

352735

AN:

1223116

Hom.:

54581

Cov.:

AF XY:

0.289

AC XY:

179271

AN XY:

620024

show subpopulations

African (AFR)

AF:

0.0595

AC:

1712

AN:

28782

American (AMR)

AF:

0.123

AC:

5419

AN:

43988

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

4639

AN:

24516

East Asian (EAS)

AF:

0.0887

AC:

3414

AN:

38486

South Asian (SAS)

AF:

0.246

AC:

19822

AN:

80668

European-Finnish (FIN)

AF:

0.273

AC:

14395

AN:

52824

Middle Eastern (MID)

AF:

0.193

AC:

708

AN:

3672

European-Non Finnish (NFE)

AF:

0.323

AC:

289561

AN:

897820

Other (OTH)

AF:

0.250

AC:

13065

AN:

52360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

11851

23701

35552

47402

59253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8276

16552

24828

33104

41380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.213

AC:

32296

AN:

151746

Hom.:

4350

Cov.:

AF XY:

0.209

AC XY:

15491

AN XY:

74102

show subpopulations

African (AFR)

AF:

0.0636

AC:

2637

AN:

41444

American (AMR)

AF:

0.172

AC:

2615

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.182

AC:

633

AN:

3470

East Asian (EAS)

AF:

0.0866

AC:

448

AN:

5176

South Asian (SAS)

AF:

0.222

AC:

1059

AN:

4772

European-Finnish (FIN)

AF:

0.267

AC:

2803

AN:

10480

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.316

AC:

21477

AN:

67864

Other (OTH)

AF:

0.194

AC:

409

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1146

2293

3439

4586

5732

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

362

724

1086

1448

1810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.277

Hom.:

11842

Bravo

AF:

0.197

Asia WGS

AF:

0.122

AC:

426

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.23

(source)

DANN

Benign

0.32

PhyloP100

-0.65

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over