dbSNP rs4821494: TXN2:c.-183C>A (chr22-36482113-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000884008.1(TXN2):c.-183C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 148,838 control chromosomes in the GnomAD database, including 27,173 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 0.58 ( 27166 hom., cov: 22)

Exomes 𝑓: 0.52 ( 7 hom. )

Consequence

TXN2
ENST00000884008.1 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.347

Publications

12 publications found

Variant links:

Genes affected

TXN2 (HGNC:17772): (thioredoxin 2) This nuclear gene encodes a mitochondrial member of the thioredoxin family, a group of small multifunctional redox-active proteins. The encoded protein may play important roles in the regulation of the mitochondrial membrane potential and in protection against oxidant-induced apoptosis. [provided by RefSeq, Jul 2008]

TXN2 Gene-Disease associations (from GenCC):

combined oxidative phosphorylation defect type 29
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
combined oxidative phosphorylation deficiency 29
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

TXN2 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=-0.78).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000884008.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXN2	ENST00000884008.1		c.-183C>A		upstream_gene	N/A	ENSP00000554067.1

Frequencies

GnomAD3 genomes

AF:

0.583

AC:

86692

AN:

148684

Hom.:

27159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.388

Gnomad AMI

AF:

0.773

Gnomad AMR

AF:

0.678

Gnomad ASJ

AF:

0.589

Gnomad EAS

AF:

0.255

Gnomad SAS

AF:

0.343

Gnomad FIN

AF:

0.615

Gnomad MID

AF:

0.558

Gnomad NFE

AF:

0.712

Gnomad OTH

AF:

0.619

GnomAD4 exome

AF:

0.522

AC:

AN:

Hom.:

AF XY:

0.474

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.412

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.833

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.583

AC:

86724

AN:

148792

Hom.:

27166

Cov.:

AF XY:

0.575

AC XY:

41660

AN XY:

72470

show subpopulations

African (AFR)

AF:

0.388

AC:

15648

AN:

40348

American (AMR)

AF:

0.679

AC:

10073

AN:

14842

Ashkenazi Jewish (ASJ)

AF:

0.589

AC:

2028

AN:

3446

East Asian (EAS)

AF:

0.254

AC:

1280

AN:

5038

South Asian (SAS)

AF:

0.344

AC:

1609

AN:

4682

European-Finnish (FIN)

AF:

0.615

AC:

6252

AN:

10164

Middle Eastern (MID)

AF:

0.559

AC:

161

AN:

288

European-Non Finnish (NFE)

AF:

0.712

AC:

47728

AN:

67050

Other (OTH)

AF:

0.615

AC:

1257

AN:

2044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1487

2973

4460

5946

7433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

704

1408

2112

2816

3520

<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:

0.615

Hom.:

4486

Bravo

AF:

0.585

Asia WGS

AF:

0.327

AC:

1138

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.4

(source)

DANN

Benign

0.65

PhyloP100

-0.35

PromoterAI

0.031

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over