rs4135179

Variant names:

• chr9-110253720-T-C
• rs4135179
• NM_003329.4:c.25-2258A>G

Variant summary

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

The NM_003329.4(TXN):​c.25-2258A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,252 control chromosomes in the GnomAD database, including 1,764 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 0.13 (1764 hom., cov: 32)
• Consequence: TXN NM_003329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) 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.25-2258A>G		intron_variant	Intron 1 of 4	ENST00000374517.6	NP_003320.2
TXN	NM_001244938.2	c.25-2258A>G		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.25-2258A>G		intron_variant	Intron 1 of 4	1	NM_003329.4	ENSP00000363641.5
TXN	ENST00000374515.9	c.25-2258A>G		intron_variant	Intron 1 of 3	1		ENSP00000363639.5

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20104 AN: 152134 Hom.: 1764 Cov.: 32

Gnomad AFR AF: 0.0357

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0606

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.132 AC: 20102 AN: 152252 Hom.: 1764 Cov.: 32 AF XY: 0.126 AC XY: 9404 AN XY: 74442

African (AFR) AF: 0.0356 AC: 1480 AN: 41540

American (AMR) AF: 0.104 AC: 1589 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 419 AN: 3472

East Asian (EAS) AF: 0.0606 AC: 314 AN: 5182

South Asian (SAS) AF: 0.133 AC: 644 AN: 4824

European-Finnish (FIN) AF: 0.105 AC: 1115 AN: 10610

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14140 AN: 68008

Other (OTH) AF: 0.108 AC: 229 AN: 2114

Alfa AF: 0.179 Hom.: 6769

Bravo AF: 0.125

Asia WGS AF: 0.0770 AC: 268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.0
DANN	Benign	0.61
PhyloP100		0.16
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: rs4135179; hg19: chr9-113016000; COSMIC: COSV65730978;