NM_003329.4:c.189+2250G>C

Variant names:

• chr9-110248570-C-G
• rs4135203
• NM_003329.4:c.189+2250G>C

Variant summary

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

The NM_003329.4(TXN):​c.189+2250G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 151,954 control chromosomes in the GnomAD database, including 4,866 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 0.23 (4866 hom., cov: 31)
• Consequence: TXN NM_003329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.649
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXN	NM_003329.4	c.189+2250G>C		intron_variant	Intron 3 of 4	ENST00000374517.6	NP_003320.2
TXN	NM_001244938.2	c.129+2788G>C		intron_variant	Intron 2 of 3		NP_001231867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXN	ENST00000374517.6	c.189+2250G>C		intron_variant	Intron 3 of 4	1	NM_003329.4	ENSP00000363641.5
TXN	ENST00000374515.9	c.129+2788G>C		intron_variant	Intron 2 of 3	1		ENSP00000363639.5

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34725 AN: 151836 Hom.: 4857 Cov.: 31

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.229 AC: 34752 AN: 151954 Hom.: 4866 Cov.: 31 AF XY: 0.238 AC XY: 17657 AN XY: 74260

African (AFR) AF: 0.123 AC: 5105 AN: 41484

American (AMR) AF: 0.325 AC: 4949 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 601 AN: 3468

East Asian (EAS) AF: 0.619 AC: 3199 AN: 5166

South Asian (SAS) AF: 0.379 AC: 1828 AN: 4824

European-Finnish (FIN) AF: 0.273 AC: 2870 AN: 10530

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15357 AN: 67934

Other (OTH) AF: 0.214 AC: 451 AN: 2112

Alfa AF: 0.133 Hom.: 234

Bravo AF: 0.231

Asia WGS AF: 0.481 AC: 1671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.32
PhyloP100		-0.65
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: rs4135203; hg19: chr9-113010850; COSMIC: COSV65730963; COSMIC: COSV65730963;