Genetic Variant TXN2:p.Ala12Gly (chr22-36480803-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012473.4(TXN2):c.35C>G(p.Ala12Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000249 in 1,603,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A12V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TXN2
NM_012473.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.00

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20376039).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012473.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXN2	NM_012473.4	MANE Select	c.35C>G	p.Ala12Gly	missense	Exon 2 of 4	NP_036605.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TXN2	ENST00000216185.7	TSL:1 MANE Select	c.35C>G	p.Ala12Gly	missense	Exon 2 of 4	ENSP00000216185.2
TXN2	ENST00000403313.5	TSL:3	c.35C>G	p.Ala12Gly	missense	Exon 2 of 4	ENSP00000385393.1
TXN2	ENST00000411915.1	TSL:5	n.35C>G		non_coding_transcript_exon	Exon 2 of 5	ENSP00000409407.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00000413

AC:

AN:

241872

AF XY:

0.00000764

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000307

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1451176

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

721142

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33134

American (AMR)

AF:

0.0000232

AC:

AN:

43128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25364

East Asian (EAS)

AF:

0.00

AC:

AN:

39556

South Asian (SAS)

AF:

0.00

AC:

AN:

85410

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53122

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

9.04e-7

AC:

AN:

1105920

Other (OTH)

AF:

0.0000167

AC:

AN:

59864

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000657

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.55

M_CAP

Benign

0.0090

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

PhyloP100

7.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.4

REVEL

Benign

0.090

Sift

Benign

0.040

Sift4G

Benign

0.24

Polyphen

0.047

Vest4

0.23

MutPred

0.25

Loss of stability (P = 0.0469)

MVP

0.36

MPC

0.25

ClinPred

0.58

GERP RS

5.6

Varity_R

0.087

gMVP

0.39

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over