rs4135212

Positions:

• chr9-110246143-C-T

Variant summary

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

The NM_003329.4(TXN):​c.190-1300G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,164 control chromosomes in the GnomAD database, including 1,130 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 (1130 hom., cov: 31)
• Consequence: TXN NM_003329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.925

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXN	NM_003329.4	c.190-1300G>A		intron_variant		ENST00000374517.6	NP_003320.2
TXN	NM_001244938.2	c.130-1300G>A		intron_variant			NP_001231867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXN	ENST00000374517.6	c.190-1300G>A		intron_variant		1	NM_003329.4	ENSP00000363641	P1
TXN	ENST00000374515.9	c.130-1300G>A		intron_variant		1		ENSP00000363639

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16633 AN: 152046 Hom.: 1132 Cov.: 31

Gnomad AFR AF: 0.0369

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.0818

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0671

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.0938

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

GnomAD4 genome AF: 0.109 AC: 16633 AN: 152164 Hom.: 1130 Cov.: 31 AF XY: 0.109 AC XY: 8115 AN XY: 74374

Gnomad4 AFR AF: 0.0371

Gnomad4 AMR AF: 0.0817

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.0657

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.0947

Alfa AF: 0.133 Hom.: 186

Bravo AF: 0.0984

Asia WGS AF: 0.134 AC: 467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.50

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: rs4135212; hg19: chr9-113008423;