rs6519008

Positions:

• chr22-36471689-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.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

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=-0.93).
• 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/exons	MANE	UniProt
TXN2	NM_012473.4	c.388-3772T>G		intron_variant		ENST00000216185.7
TXN2	XM_006724226.2	c.388-3772T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXN2	ENST00000216185.7	c.388-3772T>G		intron_variant		1	NM_012473.4	P1

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

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.0442

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.145

Alfa AF: 0.127 Hom.: 719

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

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: rs6519008; hg19: chr22-36867736;