9-110245009-T-G

Position:

• chr9-110245009-T-G

Variant summary

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

The NM_003329.4(TXN):​c.190-166A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 482,716 control chromosomes in the GnomAD database, including 85,720 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 0.59 (27744 hom., cov: 32)
  • Exomes 𝑓: 0.58 (57976 hom.)
• Consequence: TXN NM_003329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135

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]

TXN (HGNC:):

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 = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXN	NM_003329.4	c.190-166A>C		intron_variant		ENST00000374517.6	NP_003320.2
TXN	NM_001244938.2	c.130-166A>C		intron_variant			NP_001231867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXN	ENST00000374517.6	c.190-166A>C		intron_variant		1	NM_003329.4	ENSP00000363641.5
TXN	ENST00000374515.9	c.130-166A>C		intron_variant		1		ENSP00000363639.5
TXN	ENST00000487892.1	n.108A>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90138 AN: 151840 Hom.: 27701 Cov.: 32

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.611

GnomAD4 exome AF: 0.575 AC: 190346 AN: 330758 Hom.: 57976 Cov.: 4 AF XY: 0.578 AC XY: 100823 AN XY: 174554

Gnomad4 AFR exome AF: 0.695

Gnomad4 AMR exome AF: 0.722

Gnomad4 ASJ exome AF: 0.533

Gnomad4 EAS exome AF: 0.925

Gnomad4 SAS exome AF: 0.632

Gnomad4 FIN exome AF: 0.474

Gnomad4 NFE exome AF: 0.518

Gnomad4 OTH exome AF: 0.574

GnomAD4 genome AF: 0.594 AC: 90239 AN: 151958 Hom.: 27744 Cov.: 32 AF XY: 0.596 AC XY: 44230 AN XY: 74260

Gnomad4 AFR AF: 0.695

Gnomad4 AMR AF: 0.680

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.613

Alfa AF: 0.564 Hom.: 8305

Bravo AF: 0.619

Asia WGS AF: 0.751 AC: 2606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.5
DANN	Benign	0.67

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: rs4135220; hg19: chr9-113007289;