dbSNP rs4135218: TXN:c.190-238A>G (chr9-110245081-T-C) – 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.190-238A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 331,572 control chromosomes in the GnomAD database, including 37,642 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 0.49 ( 19458 hom., cov: 31)

Exomes 𝑓: 0.44 ( 18184 hom. )

Consequence

TXN
NM_003329.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.41

Publications

9 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003329.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXN	NM_003329.4	MANE Select	c.190-238A>G		intron	N/A	NP_003320.2	H9ZYJ2
	TXN	NM_001244938.2		c.130-238A>G		intron	N/A	NP_001231867.1	P10599-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TXN	ENST00000374517.6	TSL:1 MANE Select	c.190-238A>G	intron	N/A	ENSP00000363641.5	P10599-1
TXN	ENST00000374515.9	TSL:1	c.130-238A>G	intron	N/A	ENSP00000363639.5	P10599-2
TXN	ENST00000879759.1		c.178-238A>G	intron	N/A	ENSP00000549818.1

Frequencies

GnomAD3 genomes

AF:

0.492

AC:

74665

AN:

151880

Hom.:

19437

Cov.:

show subpopulations

Gnomad AFR

AF:

0.673

Gnomad AMI

AF:

0.391

Gnomad AMR

AF:

0.442

Gnomad ASJ

AF:

0.467

Gnomad EAS

AF:

0.352

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.322

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.436

Gnomad OTH

AF:

0.509

GnomAD4 exome

AF:

0.442

AC:

79372

AN:

179574

Hom.:

18184

Cov.:

AF XY:

0.442

AC XY:

42116

AN XY:

95300

show subpopulations

African (AFR)

AF:

0.679

AC:

4501

AN:

6632

American (AMR)

AF:

0.399

AC:

3825

AN:

9596

Ashkenazi Jewish (ASJ)

AF:

0.481

AC:

2597

AN:

5396

East Asian (EAS)

AF:

0.337

AC:

4485

AN:

13290

South Asian (SAS)

AF:

0.438

AC:

9292

AN:

21218

European-Finnish (FIN)

AF:

0.360

AC:

3159

AN:

8782

Middle Eastern (MID)

AF:

0.539

AC:

921

AN:

1708

European-Non Finnish (NFE)

AF:

0.446

AC:

45831

AN:

102708

Other (OTH)

AF:

0.465

AC:

4761

AN:

10244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

2139

4279

6418

8558

10697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

344

688

1032

1376

1720

<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:

0.492

AC:

74733

AN:

151998

Hom.:

19458

Cov.:

AF XY:

0.483

AC XY:

35919

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.673

AC:

27882

AN:

41430

American (AMR)

AF:

0.441

AC:

6734

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.467

AC:

1622

AN:

3470

East Asian (EAS)

AF:

0.351

AC:

1818

AN:

5174

South Asian (SAS)

AF:

0.426

AC:

2050

AN:

4812

European-Finnish (FIN)

AF:

0.322

AC:

3399

AN:

10554

Middle Eastern (MID)

AF:

0.503

AC:

148

AN:

294

European-Non Finnish (NFE)

AF:

0.436

AC:

29648

AN:

67976

Other (OTH)

AF:

0.509

AC:

1076

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1865

3730

5595

7460

9325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

658

1316

1974

2632

3290

<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:

0.459

Hom.:

10247

Bravo

AF:

0.508

Asia WGS

AF:

0.400

AC:

1390

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.2

(source)

DANN

Benign

0.42

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over