rs4135187

Variant names:

• chr9-110252488-A-T
• rs4135187
• NM_003329.4:c.25-1026T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003329.4(TXN):​c.25-1026T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,100 control chromosomes in the GnomAD database, including 1,030 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 (1030 hom., cov: 32)
• Consequence: TXN NM_003329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXN	NM_003329.4	c.25-1026T>A		intron_variant	Intron 1 of 4	ENST00000374517.6	NP_003320.2
TXN	NM_001244938.2	c.25-1026T>A		intron_variant	Intron 1 of 3		NP_001231867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXN	ENST00000374517.6	c.25-1026T>A		intron_variant	Intron 1 of 4	1	NM_003329.4	ENSP00000363641.5
TXN	ENST00000374515.9	c.25-1026T>A		intron_variant	Intron 1 of 3	1		ENSP00000363639.5

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16917 AN: 151982 Hom.: 1027 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0928

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.111 AC: 16950 AN: 152100 Hom.: 1030 Cov.: 32 AF XY: 0.112 AC XY: 8340 AN XY: 74352

African (AFR) AF: 0.109 AC: 4539 AN: 41494

American (AMR) AF: 0.0926 AC: 1416 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 352 AN: 3472

East Asian (EAS) AF: 0.215 AC: 1114 AN: 5170

South Asian (SAS) AF: 0.140 AC: 675 AN: 4818

European-Finnish (FIN) AF: 0.102 AC: 1081 AN: 10568

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7364 AN: 67976

Other (OTH) AF: 0.125 AC: 264 AN: 2110

Alfa AF: 0.108 Hom.: 115

Bravo AF: 0.108

Asia WGS AF: 0.169 AC: 591 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.82
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4135187; hg19: chr9-113014768;