rs5756202

Positions:

• chr22-36474798-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012473.4(TXN2):​c.387+1935T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 151,902 control chromosomes in the GnomAD database, including 2,991 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 0.19 (2991 hom., cov: 33)
• Consequence: TXN2 NM_012473.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.842

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXN2	NM_012473.4	c.387+1935T>G		intron_variant		ENST00000216185.7
TXN2	XM_006724226.2	c.387+1935T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXN2	ENST00000216185.7	c.387+1935T>G		intron_variant		1	NM_012473.4	P1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28623 AN: 151784 Hom.: 2985 Cov.: 33

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.0936

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.189 AC: 28649 AN: 151902 Hom.: 2991 Cov.: 33 AF XY: 0.186 AC XY: 13768 AN XY: 74216

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.0935

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.176

Alfa AF: 0.163 Hom.: 4359

Bravo AF: 0.190

Asia WGS AF: 0.149 AC: 519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.85
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs5756202; hg19: chr22-36870845;