rs5756202

Variant names:

• chr22-36474798-A-C
• rs5756202
• NM_012473.4:c.387+1935T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012473.4(TXN2):​c.387+1935T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 151,902 control chromosomes in the GnomAD database, including 2,991 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 0.19 (2991 hom., cov: 33)
• Consequence: TXN2 NM_012473.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.842
• Publications: 10 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

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.387+1935T>G		intron	N/A	NP_036605.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXN2	ENST00000216185.7	TSL:1 MANE Select	c.387+1935T>G		intron	N/A	ENSP00000216185.2
	TXN2	ENST00000403313.5	TSL:3	c.387+1935T>G		intron	N/A	ENSP00000385393.1
	TXN2	ENST00000416967.1	TSL:2	c.81+1935T>G		intron	N/A	ENSP00000469160.1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28623 AN: 151784 Hom.: 2985 Cov.: 33

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.0936

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.174

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.189 AC: 28649 AN: 151902 Hom.: 2991 Cov.: 33 AF XY: 0.186 AC XY: 13768 AN XY: 74216

African (AFR) AF: 0.278 AC: 11528 AN: 41394

American (AMR) AF: 0.118 AC: 1796 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 468 AN: 3468

East Asian (EAS) AF: 0.152 AC: 787 AN: 5162

South Asian (SAS) AF: 0.0935 AC: 449 AN: 4802

European-Finnish (FIN) AF: 0.153 AC: 1615 AN: 10538

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11302 AN: 67956

Other (OTH) AF: 0.176 AC: 372 AN: 2110

Alfa AF: 0.170 Hom.: 10237

Bravo AF: 0.190

Asia WGS AF: 0.149 AC: 519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.85
DANN	Benign	0.47
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5756202; hg19: chr22-36870845;