rs4135192

chr9-110251308-A-Gchr9-110251308-A-T

Variant summary

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

The NM_003329.4(TXN):c.129+50T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,374,862 control chromosomes in the GnomAD database, including 58,931 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 0.21 (4350 hom., cov: 29)
  • Exomes 𝑓: 0.29 (54581 hom.)
• Consequence: TXN NM_003329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646

Genes affected

TXN (HGNC:12435): (thioredoxin) The protein encoded by this gene acts as a homodimer and is involved in many redox reactions. The encoded protein is active in the reversible S-nitrosylation of cysteines in certain proteins, which is part of the response to intracellular nitric oxide. This protein is found in the cytoplasm. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXN	NM_003329.4	c.129+50T>C		intron_variant		ENST00000374517.6
TXN	NM_001244938.2	c.129+50T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXN	ENST00000374517.6	c.129+50T>C		intron_variant		1	NM_003329.4	P1
TXN	ENST00000374515.9	c.129+50T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32296 AN: 151630 Hom.: 4348 Cov.: 29

Gnomad AFR AF: 0.0638

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.0865

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.195

GnomAD3 exomes AF: 0.235 AC: 57490 AN: 244654 Hom.: 7774 AF XY: 0.245 AC XY: 32358 AN XY: 132034

Gnomad AFR exome AF: 0.0591

Gnomad AMR exome AF: 0.118

Gnomad ASJ exome AF: 0.197

Gnomad EAS exome AF: 0.0825

Gnomad SAS exome AF: 0.243

Gnomad FIN exome AF: 0.266

Gnomad NFE exome AF: 0.316

Gnomad OTH exome AF: 0.239

GnomAD4 exome AF: 0.288 AC: 352735 AN: 1223116 Hom.: 54581 Cov.: 16 AF XY: 0.289 AC XY: 179271 AN XY: 620024

Gnomad4 AFR exome AF: 0.0595

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.189

Gnomad4 EAS exome AF: 0.0887

Gnomad4 SAS exome AF: 0.246

Gnomad4 FIN exome AF: 0.273

Gnomad4 NFE exome AF: 0.323

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.213 AC: 32296 AN: 151746 Hom.: 4350 Cov.: 29 AF XY: 0.209 AC XY: 15491 AN XY: 74102

Gnomad4 AFR AF: 0.0636

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.0866

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.194

Alfa AF: 0.283 Hom.: 9147

Bravo AF: 0.197

Asia WGS AF: 0.122 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.23
Dann	Benign	0.32

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: rs4135192; hg19: chr9-113013588; COSMIC: COSV65730971;