9-110254605-T-C

Position:

• chr9-110254605-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• 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/exons	MANE	UniProt
TXN	NM_003329.4	c.24+1807A>G		intron_variant		ENST00000374517.6
TXN	NM_001244938.2	c.24+1807A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXN	ENST00000374517.6	c.24+1807A>G		intron_variant		1	NM_003329.4	P1
TXN	ENST00000374515.9	c.24+1807A>G		intron_variant		1

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

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.0704

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.224

Alfa AF: 0.248 Hom.: 6517

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

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: rs4135168; hg19: chr9-113016885;