dbSNP rs4135221: TXN:c.190-114C>T (chr9-110244957-G-A) – 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.190-114C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 687,600 control chromosomes in the GnomAD database, including 4,496 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 0.12 ( 1135 hom., cov: 32)

Exomes 𝑓: 0.11 ( 3361 hom. )

Consequence

TXN
NM_003329.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.838

Publications

6 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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXN	NM_003329.4 link	c.190-114C>T		intron_variant	Intron 3 of 4	ENST00000374517.6	NP_003320.2	P10599-1H9ZYJ2
TXN	NM_001244938.2 link	c.130-114C>T		intron_variant	Intron 2 of 3		NP_001231867.1	P10599-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TXN	ENST00000374517.6 link	c.190-114C>T	intron_variant	Intron 3 of 4	1	NM_003329.4	ENSP00000363641.5	P10599-1
TXN	ENST00000374515.9 link	c.130-114C>T	intron_variant	Intron 2 of 3	1		ENSP00000363639.5	P10599-2
TXN	ENST00000487892.1 link	n.160C>T	non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17690

AN:

151984

Hom.:

1135

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.0763

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.0501

Gnomad SAS

AF:

0.0855

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.104

GnomAD4 exome

AF:

0.108

AC:

57769

AN:

535498

Hom.:

3361

Cov.:

AF XY:

0.108

AC XY:

30743

AN XY:

285748

show subpopulations

African (AFR)

AF:

0.150

AC:

2228

AN:

14830

American (AMR)

AF:

0.0610

AC:

1685

AN:

27606

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

1983

AN:

15040

East Asian (EAS)

AF:

0.0455

AC:

1454

AN:

31930

South Asian (SAS)

AF:

0.0894

AC:

4216

AN:

47168

European-Finnish (FIN)

AF:

0.106

AC:

4558

AN:

43168

Middle Eastern (MID)

AF:

0.168

AC:

600

AN:

3582

European-Non Finnish (NFE)

AF:

0.117

AC:

37955

AN:

325546

Other (OTH)

AF:

0.116

AC:

3090

AN:

26628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

2427

4855

7282

9710

12137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

656

1312

1968

2624

3280

<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:

0.116

AC:

17698

AN:

152102

Hom.:

1135

Cov.:

AF XY:

0.115

AC XY:

8514

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.149

AC:

6160

AN:

41474

American (AMR)

AF:

0.0762

AC:

1165

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

459

AN:

3470

East Asian (EAS)

AF:

0.0500

AC:

259

AN:

5176

South Asian (SAS)

AF:

0.0851

AC:

411

AN:

4828

European-Finnish (FIN)

AF:

0.103

AC:

1090

AN:

10582

Middle Eastern (MID)

AF:

0.154

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.114

AC:

7730

AN:

67976

Other (OTH)

AF:

0.102

AC:

216

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

792

1583

2375

3166

3958

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

204

408

612

816

1020

<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:

0.113

Hom.:

714

Bravo

AF:

0.115

Asia WGS

AF:

0.0690

AC:

242

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.5

(source)

DANN

Benign

0.67

PhyloP100

0.84

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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