chr9-110254605-T-C

Variant names:

• chr9-110254605-T-C
• rs4135168
• NM_003329.4:c.24+1807A>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+1807A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,192 control chromosomes in the GnomAD database, including 5,002 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 0.25 (5002 hom., cov: 33)
• Consequence: TXN NM_003329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 21 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 (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXN	NM_003329.4	c.24+1807A>G		intron_variant	Intron 1 of 4	ENST00000374517.6	NP_003320.2
TXN	NM_001244938.2	c.24+1807A>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+1807A>G		intron_variant	Intron 1 of 4	1	NM_003329.4	ENSP00000363641.5
TXN	ENST00000374515.9	c.24+1807A>G		intron_variant	Intron 1 of 3	1		ENSP00000363639.5

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38126 AN: 152074 Hom.: 4996 Cov.: 33

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.0712

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.251 AC: 38154 AN: 152192 Hom.: 5002 Cov.: 33 AF XY: 0.252 AC XY: 18738 AN XY: 74406

African (AFR) AF: 0.268 AC: 11110 AN: 41528

American (AMR) AF: 0.240 AC: 3674 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 749 AN: 3470

East Asian (EAS) AF: 0.0704 AC: 365 AN: 5186

South Asian (SAS) AF: 0.216 AC: 1043 AN: 4824

European-Finnish (FIN) AF: 0.309 AC: 3264 AN: 10580

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17076 AN: 67998

Other (OTH) AF: 0.224 AC: 472 AN: 2110

Alfa AF: 0.250 Hom.: 14713

Bravo AF: 0.249

Asia WGS AF: 0.160 AC: 557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.64
PhyloP100		-1.1
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: rs4135168; hg19: chr9-113016885;