NM_012473.4:c.387+3892A>G

Variant names:

• chr22-36472841-T-C
• rs9622400
• NM_012473.4:c.387+3892A>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+3892A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0538 in 152,186 control chromosomes in the GnomAD database, including 330 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 0.054 (330 hom., cov: 32)
• Consequence: TXN2 NM_012473.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0839 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+3892A>G		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+3892A>G		intron	N/A	ENSP00000216185.2	Q99757
	TXN2	ENST00000403313.5	TSL:3	c.387+3892A>G		intron	N/A	ENSP00000385393.1	Q99757
	TXN2	ENST00000884007.1		c.387+3892A>G		intron	N/A	ENSP00000554066.1

Frequencies

GnomAD3 genomes AF: 0.0538 AC: 8181 AN: 152068 Hom.: 329 Cov.: 32

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.0368

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0181

Gnomad FIN AF: 0.0676

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0857

Gnomad OTH AF: 0.0495

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

GnomAD4 genome AF: 0.0538 AC: 8183 AN: 152186 Hom.: 330 Cov.: 32 AF XY: 0.0526 AC XY: 3917 AN XY: 74402

African (AFR) AF: 0.0147 AC: 612 AN: 41538

American (AMR) AF: 0.0367 AC: 561 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 86 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.0185 AC: 89 AN: 4814

European-Finnish (FIN) AF: 0.0676 AC: 717 AN: 10604

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0857 AC: 5829 AN: 68002

Other (OTH) AF: 0.0490 AC: 103 AN: 2104

Alfa AF: 0.0697 Hom.: 516

Bravo AF: 0.0492

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.40
PhyloP100		-0.28
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: rs9622400; hg19: chr22-36868888;