rs8136921

Positions:

• chr22-36471892-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXN2	NM_012473.4	c.388-3975A>G		intron_variant		ENST00000216185.7	NP_036605.2
TXN2	XM_006724226.2	c.388-3975A>G		intron_variant			XP_006724289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXN2	ENST00000216185.7	c.388-3975A>G		intron_variant		1	NM_012473.4	ENSP00000216185.2

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

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.0451

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.195

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.1
DANN	Benign	0.22

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: rs8136921; hg19: chr22-36867939; COSMIC: COSV53398442;