9-110251071-C-T

Position:

• chr9-110251071-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003329.4(TXN):​c.130-192G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 151,870 control chromosomes in the GnomAD database, including 9,674 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 0.34 (9674 hom., cov: 31)
• Consequence: TXN NM_003329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXN	NM_003329.4	c.130-192G>A		intron_variant		ENST00000374517.6	NP_003320.2
TXN	NM_001244938.2	c.129+287G>A		intron_variant			NP_001231867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXN	ENST00000374517.6	c.130-192G>A		intron_variant		1	NM_003329.4	ENSP00000363641.5
TXN	ENST00000374515.9	c.129+287G>A		intron_variant		1		ENSP00000363639.5

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51775 AN: 151754 Hom.: 9651 Cov.: 31

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.341 AC: 51855 AN: 151870 Hom.: 9674 Cov.: 31 AF XY: 0.343 AC XY: 25456 AN XY: 74214

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.330

Alfa AF: 0.293 Hom.: 3588

Bravo AF: 0.362

Asia WGS AF: 0.493 AC: 1713 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.56
DANN	Benign	0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs2418076; hg19: chr9-113013351;