22-36474424-T-C

Variant names:

• chr22-36474424-T-C
• rs2267337
• NM_012473.4:c.387+2309A>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+2309A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 152,094 control chromosomes in the GnomAD database, including 45,321 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 0.76 (45321 hom., cov: 31)
• Consequence: TXN2 NM_012473.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• Publications: 6 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.807 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+2309A>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+2309A>G		intron	N/A	ENSP00000216185.2
	TXN2	ENST00000403313.5	TSL:3	c.387+2309A>G		intron	N/A	ENSP00000385393.1
	TXN2	ENST00000416967.1	TSL:2	c.81+2309A>G		intron	N/A	ENSP00000469160.1

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116051 AN: 151976 Hom.: 45293 Cov.: 31

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.769

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

GnomAD4 genome AF: 0.764 AC: 116133 AN: 152094 Hom.: 45321 Cov.: 31 AF XY: 0.754 AC XY: 56083 AN XY: 74344

African (AFR) AF: 0.766 AC: 31791 AN: 41488

American (AMR) AF: 0.795 AC: 12141 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2775 AN: 3470

East Asian (EAS) AF: 0.259 AC: 1339 AN: 5172

South Asian (SAS) AF: 0.521 AC: 2511 AN: 4820

European-Finnish (FIN) AF: 0.725 AC: 7660 AN: 10566

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55280 AN: 67988

Other (OTH) AF: 0.763 AC: 1610 AN: 2110

Alfa AF: 0.797 Hom.: 6403

Bravo AF: 0.770

Asia WGS AF: 0.421 AC: 1464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.8
DANN	Benign	0.37
PhyloP100		-0.18
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: rs2267337; hg19: chr22-36870471;