rs9622400

chr22-36472841-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.387+3892A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0538 in 152,186 control chromosomes in the GnomAD database, including 330 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 0.054 (330 hom., cov: 32)
• Consequence: TXN2 NM_012473.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXN2	NM_012473.4	c.387+3892A>G		intron_variant		ENST00000216185.7
TXN2	XM_006724226.2	c.387+3892A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXN2	ENST00000216185.7	c.387+3892A>G		intron_variant		1	NM_012473.4	P1

Frequencies

GnomAD3 genomes AF: 0.0538 AC: 8181 AN: 152068 Hom.: 329 Cov.: 32

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.0368

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0181

Gnomad FIN AF: 0.0676

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0857

Gnomad OTH AF: 0.0495

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

GnomAD4 genome AF: 0.0538 AC: 8183 AN: 152186 Hom.: 330 Cov.: 32 AF XY: 0.0526 AC XY: 3917 AN XY: 74402

Gnomad4 AFR AF: 0.0147

Gnomad4 AMR AF: 0.0367

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0185

Gnomad4 FIN AF: 0.0676

Gnomad4 NFE AF: 0.0857

Gnomad4 OTH AF: 0.0490

Alfa AF: 0.0726 Hom.: 404

Bravo AF: 0.0492

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.2
Dann	Benign	0.40

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: rs9622400; hg19: chr22-36868888;