chr9-110255282-G-A

Variant names:

• chr9-110255282-G-A
• rs4135165
• NM_003329.4:c.24+1130C>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.24+1130C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0889 in 152,244 control chromosomes in the GnomAD database, including 685 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 0.089 (685 hom., cov: 32)
• Consequence: TXN NM_003329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• Publications: 11 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXN	NM_003329.4	c.24+1130C>T		intron_variant	Intron 1 of 4	ENST00000374517.6	NP_003320.2
TXN	NM_001244938.2	c.24+1130C>T		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+1130C>T		intron_variant	Intron 1 of 4	1	NM_003329.4	ENSP00000363641.5
TXN	ENST00000374515.9	c.24+1130C>T		intron_variant	Intron 1 of 3	1		ENSP00000363639.5

Frequencies

GnomAD3 genomes AF: 0.0889 AC: 13530 AN: 152126 Hom.: 686 Cov.: 32

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0759

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0233

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0958

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.0889 AC: 13536 AN: 152244 Hom.: 685 Cov.: 32 AF XY: 0.0865 AC XY: 6441 AN XY: 74452

African (AFR) AF: 0.0915 AC: 3802 AN: 41548

American (AMR) AF: 0.0758 AC: 1159 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 726 AN: 3466

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5182

South Asian (SAS) AF: 0.149 AC: 717 AN: 4824

European-Finnish (FIN) AF: 0.0233 AC: 247 AN: 10614

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.0958 AC: 6513 AN: 67992

Other (OTH) AF: 0.102 AC: 215 AN: 2112

Alfa AF: 0.101 Hom.: 1561

Bravo AF: 0.0917

Asia WGS AF: 0.0740 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.87
PhyloP100		-0.042
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: rs4135165; hg19: chr9-113017562;