rs4135215

chr9-110245219-T-C

Variant summary

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

The NM_003329.4(TXN):c.190-376A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 165,546 control chromosomes in the GnomAD database, including 1,417 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 0.11 (1252 hom., cov: 30)
  • Exomes 𝑓: 0.15 (165 hom.)
• Consequence: TXN NM_003329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.768

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXN	NM_003329.4	c.190-376A>G		intron_variant		ENST00000374517.6
TXN	NM_001244938.2	c.130-376A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXN	ENST00000374517.6	c.190-376A>G		intron_variant		1	NM_003329.4	P1
TXN	ENST00000374515.9	c.130-376A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17490 AN: 152028 Hom.: 1251 Cov.: 30

Gnomad AFR AF: 0.0348

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0907

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.151 AC: 2020 AN: 13400 Hom.: 165 AF XY: 0.154 AC XY: 1114 AN XY: 7220

Gnomad4 AFR exome AF: 0.0370

Gnomad4 AMR exome AF: 0.0974

Gnomad4 ASJ exome AF: 0.193

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.165

Gnomad4 NFE exome AF: 0.157

Gnomad4 OTH exome AF: 0.186

GnomAD4 genome AF: 0.115 AC: 17493 AN: 152146 Hom.: 1252 Cov.: 30 AF XY: 0.113 AC XY: 8402 AN XY: 74366

Gnomad4 AFR AF: 0.0347

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.0907

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.150

Alfa AF: 0.148 Hom.: 2187

Bravo AF: 0.115

Asia WGS AF: 0.179 AC: 621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.2
Dann	Benign	0.75

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: rs4135215; hg19: chr9-113007499;