rs8140110

Variant names:

• chr22-36472588-C-T
• rs8140110
• NM_012473.4:c.387+4145G>A

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+4145G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 151,776 control chromosomes in the GnomAD database, including 1,485 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 0.13 (1485 hom., cov: 31)
• Consequence: TXN2 NM_012473.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.760
• 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXN2	NM_012473.4	MANE Select	c.387+4145G>A		intron	N/A	NP_036605.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXN2	ENST00000216185.7	TSL:1 MANE Select	c.387+4145G>A		intron	N/A	ENSP00000216185.2	Q99757
	TXN2	ENST00000403313.5	TSL:3	c.387+4145G>A		intron	N/A	ENSP00000385393.1	Q99757
	TXN2	ENST00000884007.1		c.387+4145G>A		intron	N/A	ENSP00000554066.1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19475 AN: 151658 Hom.: 1488 Cov.: 31

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.0933

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.0959

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.128 AC: 19489 AN: 151776 Hom.: 1485 Cov.: 31 AF XY: 0.129 AC XY: 9536 AN XY: 74178

African (AFR) AF: 0.209 AC: 8633 AN: 41320

American (AMR) AF: 0.0931 AC: 1418 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 652 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5176

South Asian (SAS) AF: 0.167 AC: 803 AN: 4796

European-Finnish (FIN) AF: 0.103 AC: 1078 AN: 10506

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.0958 AC: 6514 AN: 67964

Other (OTH) AF: 0.115 AC: 243 AN: 2106

Alfa AF: 0.119 Hom.: 154

Bravo AF: 0.129

Asia WGS AF: 0.0740 AC: 257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.50
PhyloP100		-0.76
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: rs8140110; hg19: chr22-36868635;