rs8139906

Variant names:

• chr22-36472213-G-C
• rs8139906
• NM_012473.4:c.388-4296C>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.388-4296C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,130 control chromosomes in the GnomAD database, including 5,324 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 0.24 (5324 hom., cov: 32)
• Consequence: TXN2 NM_012473.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328
• Publications: 5 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)

ENSG00000294928 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXN2	NM_012473.4	c.388-4296C>G		intron_variant	Intron 3 of 3	ENST00000216185.7	NP_036605.2
TXN2	XM_006724226.2	c.388-4296C>G		intron_variant	Intron 3 of 3		XP_006724289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXN2	ENST00000216185.7	c.388-4296C>G		intron_variant	Intron 3 of 3	1	NM_012473.4	ENSP00000216185.2

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36213 AN: 152012 Hom.: 5318 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.238 AC: 36245 AN: 152130 Hom.: 5324 Cov.: 32 AF XY: 0.235 AC XY: 17487 AN XY: 74378

African (AFR) AF: 0.412 AC: 17086 AN: 41456

American (AMR) AF: 0.154 AC: 2344 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 789 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5186

South Asian (SAS) AF: 0.187 AC: 904 AN: 4826

European-Finnish (FIN) AF: 0.170 AC: 1801 AN: 10596

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12544 AN: 68012

Other (OTH) AF: 0.202 AC: 427 AN: 2112

Alfa AF: 0.229 Hom.: 553

Bravo AF: 0.241

Asia WGS AF: 0.0990 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.59
PhyloP100		-0.33
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: rs8139906; hg19: chr22-36868260;