NM_012473.4:c.388-3975A>G

Variant names:

• chr22-36471892-T-C
• rs8136921
• NM_012473.4:c.388-3975A>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.388-3975A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 150,306 control chromosomes in the GnomAD database, including 4,402 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 0.23 (4402 hom., cov: 31)
• Consequence: TXN2 NM_012473.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.422
• 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)

ENSG00000294928 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.344 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.388-3975A>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.388-3975A>G		intron	N/A	ENSP00000216185.2	Q99757
	TXN2	ENST00000403313.5	TSL:3	c.388-3975A>G		intron	N/A	ENSP00000385393.1	Q99757
	TXN2	ENST00000884007.1		c.388-3975A>G		intron	N/A	ENSP00000554066.1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34342 AN: 150196 Hom.: 4401 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.0448

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.229 AC: 34368 AN: 150306 Hom.: 4402 Cov.: 31 AF XY: 0.228 AC XY: 16709 AN XY: 73264

African (AFR) AF: 0.349 AC: 14246 AN: 40828

American (AMR) AF: 0.152 AC: 2267 AN: 14936

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 780 AN: 3464

East Asian (EAS) AF: 0.0451 AC: 229 AN: 5072

South Asian (SAS) AF: 0.211 AC: 1005 AN: 4774

European-Finnish (FIN) AF: 0.191 AC: 1947 AN: 10204

Middle Eastern (MID) AF: 0.217 AC: 63 AN: 290

European-Non Finnish (NFE) AF: 0.193 AC: 13101 AN: 67752

Other (OTH) AF: 0.195 AC: 405 AN: 2080

Alfa AF: 0.224 Hom.: 514

Bravo AF: 0.225

Asia WGS AF: 0.126 AC: 438 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	2.1
DANN	Benign	0.22
PhyloP100		-0.42
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: rs8136921; hg19: chr22-36867939; COSMIC: COSV53398442;