rs4135162

Positions:

• chr9-110255625-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_003329.4(TXN):​c.24+787G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 152,332 control chromosomes in the GnomAD database, including 28 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 0.013 (28 hom., cov: 33)
• Consequence: TXN NM_003329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0127 (1932/152332) while in subpopulation NFE AF= 0.0219 (1491/68030). AF 95% confidence interval is 0.021. There are 28 homozygotes in gnomad4. There are 857 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 28 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXN	NM_003329.4	c.24+787G>C		intron_variant		ENST00000374517.6
TXN	NM_001244938.2	c.24+787G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXN	ENST00000374517.6	c.24+787G>C		intron_variant		1	NM_003329.4	P1
TXN	ENST00000374515.9	c.24+787G>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1932 AN: 152214 Hom.: 28 Cov.: 33

Gnomad AFR AF: 0.00362

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.00379

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00687

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.00908

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

GnomAD4 genome AF: 0.0127 AC: 1932 AN: 152332 Hom.: 28 Cov.: 33 AF XY: 0.0115 AC XY: 857 AN XY: 74492

Gnomad4 AFR AF: 0.00361

Gnomad4 AMR AF: 0.00379

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00687

Gnomad4 NFE AF: 0.0219

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.0178 Hom.: 5

Bravo AF: 0.0122

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	19
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs4135162; hg19: chr9-113017905;