rs4135225

Variant names:

• chr9-110244411-G-A
• rs4135225
• NM_003329.4:c.256-192C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-110244411-G-A
• chr9-110244411-G-C
• chr9-110244411-G-T

Variant summary

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

The NM_003329.4(TXN):​c.256-192C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 150,900 control chromosomes in the GnomAD database, including 39,054 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 0.71 (39054 hom., cov: 29)
• Consequence: TXN NM_003329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXN	NM_003329.4	c.256-192C>T		intron_variant	Intron 4 of 4	ENST00000374517.6	NP_003320.2
TXN	NM_001244938.2	c.196-192C>T		intron_variant	Intron 3 of 3		NP_001231867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXN	ENST00000374517.6	c.256-192C>T		intron_variant	Intron 4 of 4	1	NM_003329.4	ENSP00000363641.5
TXN	ENST00000374515.9	c.196-192C>T		intron_variant	Intron 3 of 3	1		ENSP00000363639.5
TXN	ENST00000487892.1	n.340-192C>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.714 AC: 107676 AN: 150794 Hom.: 39001 Cov.: 29

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.778

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.667

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.714 AC: 107780 AN: 150900 Hom.: 39054 Cov.: 29 AF XY: 0.715 AC XY: 52724 AN XY: 73718

African (AFR) AF: 0.771 AC: 31739 AN: 41168

American (AMR) AF: 0.765 AC: 11575 AN: 15140

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2225 AN: 3468

East Asian (EAS) AF: 0.977 AC: 5063 AN: 5184

South Asian (SAS) AF: 0.806 AC: 3865 AN: 4796

European-Finnish (FIN) AF: 0.592 AC: 6017 AN: 10156

Middle Eastern (MID) AF: 0.675 AC: 197 AN: 292

European-Non Finnish (NFE) AF: 0.663 AC: 44907 AN: 67714

Other (OTH) AF: 0.716 AC: 1490 AN: 2080

Alfa AF: 0.695 Hom.: 4766

Bravo AF: 0.730

Asia WGS AF: 0.886 AC: 3060 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.22
PhyloP100		-0.15
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: rs4135225; hg19: chr9-113006691;