dbSNP rs4135215: TXN:c.190-376A>G (chr9-110245219-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.190-376A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 165,546 control chromosomes in the GnomAD database, including 1,417 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 0.11 ( 1252 hom., cov: 30)

Exomes 𝑓: 0.15 ( 165 hom. )

Consequence

TXN
NM_003329.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.768

Publications

10 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 (EAS) allele frequency at 95% confidence interval = 0.225 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.190-376A>G		intron	N/A	NP_003320.2	H9ZYJ2
	TXN	NM_001244938.2		c.130-376A>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.190-376A>G	intron	N/A	ENSP00000363641.5	P10599-1
TXN	ENST00000374515.9	TSL:1	c.130-376A>G	intron	N/A	ENSP00000363639.5	P10599-2
TXN	ENST00000879759.1		c.178-376A>G	intron	N/A	ENSP00000549818.1

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17490

AN:

152028

Hom.:

1251

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0348

Gnomad AMI

AF:

0.165

Gnomad AMR

AF:

0.120

Gnomad ASJ

AF:

0.190

Gnomad EAS

AF:

0.237

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.0907

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.150

Gnomad OTH

AF:

0.148

GnomAD4 exome

AF:

0.151

AC:

2020

AN:

13400

Hom.:

165

AF XY:

0.154

AC XY:

1114

AN XY:

7220

show subpopulations

African (AFR)

AF:

0.0370

AC:

AN:

540

American (AMR)

AF:

0.0974

AC:

157

AN:

1612

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

AN:

410

East Asian (EAS)

AF:

0.215

AC:

240

AN:

1114

South Asian (SAS)

AF:

0.137

AC:

205

AN:

1492

European-Finnish (FIN)

AF:

0.165

AC:

AN:

310

Middle Eastern (MID)

AF:

0.344

AC:

AN:

European-Non Finnish (NFE)

AF:

0.157

AC:

1143

AN:

7276

Other (OTH)

AF:

0.186

AC:

114

AN:

614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

177

266

354

443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.115

AC:

17493

AN:

152146

Hom.:

1252

Cov.:

AF XY:

0.113

AC XY:

8402

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.0347

AC:

1442

AN:

41532

American (AMR)

AF:

0.120

AC:

1829

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.190

AC:

660

AN:

3468

East Asian (EAS)

AF:

0.236

AC:

1219

AN:

5162

South Asian (SAS)

AF:

0.136

AC:

653

AN:

4818

European-Finnish (FIN)

AF:

0.0907

AC:

960

AN:

10580

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.150

AC:

10227

AN:

68006

Other (OTH)

AF:

0.150

AC:

317

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

754

1508

2263

3017

3771

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

194

388

582

776

970

<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:

0.144

Hom.:

2902

Bravo

AF:

0.115

Asia WGS

AF:

0.179

AC:

621

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.2

(source)

DANN

Benign

0.75

PhyloP100

0.77

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