9-110255072-T-C

Variant names:

• chr9-110255072-T-C
• rs1410051
• NM_003329.4:c.24+1340A>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.24+1340A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,002 control chromosomes in the GnomAD database, including 5,580 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 0.27 (5580 hom., cov: 33)
• Consequence: TXN NM_003329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXN	NM_003329.4	c.24+1340A>G		intron_variant	Intron 1 of 4	ENST00000374517.6	NP_003320.2
TXN	NM_001244938.2	c.24+1340A>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.24+1340A>G		intron_variant	Intron 1 of 4	1	NM_003329.4	ENSP00000363641.5
TXN	ENST00000374515.9	c.24+1340A>G		intron_variant	Intron 1 of 3	1		ENSP00000363639.5

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40349 AN: 151884 Hom.: 5572 Cov.: 33

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.266 AC: 40381 AN: 152002 Hom.: 5580 Cov.: 33 AF XY: 0.267 AC XY: 19805 AN XY: 74312

African (AFR) AF: 0.315 AC: 13061 AN: 41486

American (AMR) AF: 0.303 AC: 4621 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1093 AN: 3470

East Asian (EAS) AF: 0.128 AC: 661 AN: 5150

South Asian (SAS) AF: 0.329 AC: 1586 AN: 4814

European-Finnish (FIN) AF: 0.235 AC: 2482 AN: 10574

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.236 AC: 16062 AN: 67922

Other (OTH) AF: 0.253 AC: 535 AN: 2112

Alfa AF: 0.251 Hom.: 16687

Bravo AF: 0.274

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.36
DANN	Benign	0.38
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1410051; hg19: chr9-113017352;