rs2281082

chr22-36476703-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012473.4(TXN2):c.387+30A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 1,613,398 control chromosomes in the GnomAD database, including 492,175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (45329 hom., cov: 30)
  • Exomes 𝑓: 0.77 (446846 hom.)
• Consequence: TXN2 NM_012473.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.571

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 22-36476703-T-G is Benign according to our data. Variant chr22-36476703-T-G is described in ClinVar as [Benign]. Clinvar id is 1280669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXN2	NM_012473.4	c.387+30A>C		intron_variant		ENST00000216185.7
TXN2	XM_006724226.2	c.387+30A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXN2	ENST00000216185.7	c.387+30A>C		intron_variant		1	NM_012473.4	P1

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116052 AN: 151890 Hom.: 45302 Cov.: 30

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.771

GnomAD3 exomes AF: 0.719 AC: 180359 AN: 250778 Hom.: 67935 AF XY: 0.714 AC XY: 96711 AN XY: 135534

Gnomad AFR exome AF: 0.771

Gnomad AMR exome AF: 0.758

Gnomad ASJ exome AF: 0.789

Gnomad EAS exome AF: 0.266

Gnomad SAS exome AF: 0.548

Gnomad FIN exome AF: 0.724

Gnomad NFE exome AF: 0.811

Gnomad OTH exome AF: 0.754

GnomAD4 exome AF: 0.774 AC: 1131615 AN: 1461390 Hom.: 446846 Cov.: 50 AF XY: 0.769 AC XY: 558835 AN XY: 727020

Gnomad4 AFR exome AF: 0.770

Gnomad4 AMR exome AF: 0.764

Gnomad4 ASJ exome AF: 0.781

Gnomad4 EAS exome AF: 0.287

Gnomad4 SAS exome AF: 0.558

Gnomad4 FIN exome AF: 0.735

Gnomad4 NFE exome AF: 0.812

Gnomad4 OTH exome AF: 0.748

GnomAD4 genome AF: 0.764 AC: 116134 AN: 152008 Hom.: 45329 Cov.: 30 AF XY: 0.755 AC XY: 56100 AN XY: 74312

Gnomad4 AFR AF: 0.769

Gnomad4 AMR AF: 0.795

Gnomad4 ASJ AF: 0.799

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.813

Gnomad4 OTH AF: 0.765

Alfa AF: 0.798 Hom.: 50118

Bravo AF: 0.771

Asia WGS AF: 0.421 AC: 1465 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Combined oxidative phosphorylation deficiency 29 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.91
Dann	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2281082; hg19: chr22-36872750; COSMIC: COSV53397663;