rs6519008

Variant names:

• chr22-36471689-A-C
• rs6519008
• NM_012473.4:c.388-3772T>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.388-3772T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,130 control chromosomes in the GnomAD database, including 3,088 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 0.17 (3088 hom., cov: 32)
• Consequence: TXN2 NM_012473.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXN2	NM_012473.4	c.388-3772T>G		intron_variant	Intron 3 of 3	ENST00000216185.7	NP_036605.2
TXN2	XM_006724226.2	c.388-3772T>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.388-3772T>G		intron_variant	Intron 3 of 3	1	NM_012473.4	ENSP00000216185.2

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26284 AN: 152012 Hom.: 3089 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.0439

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.173 AC: 26309 AN: 152130 Hom.: 3088 Cov.: 32 AF XY: 0.173 AC XY: 12875 AN XY: 74382

African (AFR) AF: 0.333 AC: 13817 AN: 41480

American (AMR) AF: 0.111 AC: 1700 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 696 AN: 3472

East Asian (EAS) AF: 0.0442 AC: 229 AN: 5184

South Asian (SAS) AF: 0.190 AC: 916 AN: 4820

European-Finnish (FIN) AF: 0.118 AC: 1250 AN: 10588

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7190 AN: 67984

Other (OTH) AF: 0.145 AC: 305 AN: 2110

Alfa AF: 0.126 Hom.: 784

Bravo AF: 0.176

Asia WGS AF: 0.118 AC: 411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.41
DANN	Benign	0.20
PhyloP100		-0.79
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: rs6519008; hg19: chr22-36867736;