9-110251071-C-T

Variant names:

• chr9-110251071-C-T
• rs2418076
• NM_003329.4:c.130-192G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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 (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXN	NM_003329.4	c.130-192G>A		intron_variant	Intron 2 of 4	ENST00000374517.6	NP_003320.2
TXN	NM_001244938.2	c.129+287G>A		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.130-192G>A		intron_variant	Intron 2 of 4	1	NM_003329.4	ENSP00000363641.5
TXN	ENST00000374515.9	c.129+287G>A		intron_variant	Intron 2 of 3	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

African (AFR) AF: 0.457 AC: 18924 AN: 41378

American (AMR) AF: 0.376 AC: 5734 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 985 AN: 3464

East Asian (EAS) AF: 0.587 AC: 3032 AN: 5164

South Asian (SAS) AF: 0.399 AC: 1922 AN: 4820

European-Finnish (FIN) AF: 0.206 AC: 2172 AN: 10542

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18100 AN: 67922

Other (OTH) AF: 0.330 AC: 695 AN: 2106

Alfa AF: 0.318 Hom.: 6800

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
PhyloP100		-0.28
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: rs2418076; hg19: chr9-113013351;