Genetic Variant TXN:c.190-166A>C (chr9-110245009-T-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.190-166A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 482,716 control chromosomes in the GnomAD database, including 85,720 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 0.59 ( 27744 hom., cov: 32)

Exomes 𝑓: 0.58 ( 57976 hom. )

Consequence

TXN
NM_003329.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.135

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:

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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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 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.190-166A>C		intron	N/A	NP_003320.2	H9ZYJ2
	TXN	NM_001244938.2		c.130-166A>C		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.190-166A>C	intron	N/A	ENSP00000363641.5	P10599-1
TXN	ENST00000374515.9	TSL:1	c.130-166A>C	intron	N/A	ENSP00000363639.5	P10599-2
TXN	ENST00000879759.1		c.178-166A>C	intron	N/A	ENSP00000549818.1

Frequencies

GnomAD3 genomes

AF:

0.594

AC:

90138

AN:

151840

Hom.:

27701

Cov.:

show subpopulations

Gnomad AFR

AF:

0.695

Gnomad AMI

AF:

0.508

Gnomad AMR

AF:

0.680

Gnomad ASJ

AF:

0.520

Gnomad EAS

AF:

0.910

Gnomad SAS

AF:

0.629

Gnomad FIN

AF:

0.463

Gnomad MID

AF:

0.509

Gnomad NFE

AF:

0.511

Gnomad OTH

AF:

0.611

GnomAD4 exome

AF:

0.575

AC:

190346

AN:

330758

Hom.:

57976

Cov.:

AF XY:

0.578

AC XY:

100823

AN XY:

174554

show subpopulations

African (AFR)

AF:

0.695

AC:

7028

AN:

10118

American (AMR)

AF:

0.722

AC:

10785

AN:

14928

Ashkenazi Jewish (ASJ)

AF:

0.533

AC:

5211

AN:

9770

East Asian (EAS)

AF:

0.925

AC:

23250

AN:

25124

South Asian (SAS)

AF:

0.632

AC:

19775

AN:

31292

European-Finnish (FIN)

AF:

0.474

AC:

12239

AN:

25824

Middle Eastern (MID)

AF:

0.596

AC:

1781

AN:

2986

European-Non Finnish (NFE)

AF:

0.518

AC:

99535

AN:

192010

Other (OTH)

AF:

0.574

AC:

10742

AN:

18706

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

3584

7167

10751

14334

17918

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

724

1448

2172

2896

3620

<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:

0.594

AC:

90239

AN:

151958

Hom.:

27744

Cov.:

AF XY:

0.596

AC XY:

44230

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.695

AC:

28785

AN:

41438

American (AMR)

AF:

0.680

AC:

10379

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.520

AC:

1807

AN:

3472

East Asian (EAS)

AF:

0.911

AC:

4716

AN:

5174

South Asian (SAS)

AF:

0.629

AC:

3034

AN:

4824

European-Finnish (FIN)

AF:

0.463

AC:

4866

AN:

10520

Middle Eastern (MID)

AF:

0.524

AC:

154

AN:

294

European-Non Finnish (NFE)

AF:

0.511

AC:

34743

AN:

67958

Other (OTH)

AF:

0.613

AC:

1295

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1801

3602

5403

7204

9005

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

750

1500

2250

3000

3750

<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:

0.566

Hom.:

10365

Bravo

AF:

0.619

Asia WGS

AF:

0.751

AC:

2606

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

5.5

(source)

DANN

Benign

0.67

PhyloP100

-0.14

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over