9-110246143-C-T

Variant names:

• chr9-110246143-C-T
• rs4135212
• NM_003329.4:c.190-1300G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003329.4(TXN):​c.190-1300G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,164 control chromosomes in the GnomAD database, including 1,130 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 0.11 (1130 hom., cov: 31)
• Consequence: TXN NM_003329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.925
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXN	NM_003329.4	c.190-1300G>A		intron_variant	Intron 3 of 4	ENST00000374517.6	NP_003320.2
TXN	NM_001244938.2	c.130-1300G>A		intron_variant	Intron 2 of 3		NP_001231867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXN	ENST00000374517.6	c.190-1300G>A		intron_variant	Intron 3 of 4	1	NM_003329.4	ENSP00000363641.5
TXN	ENST00000374515.9	c.130-1300G>A		intron_variant	Intron 2 of 3	1		ENSP00000363639.5

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16633 AN: 152046 Hom.: 1132 Cov.: 31

Gnomad AFR AF: 0.0369

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.0818

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0671

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.0938

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

GnomAD4 genome AF: 0.109 AC: 16633 AN: 152164 Hom.: 1130 Cov.: 31 AF XY: 0.109 AC XY: 8115 AN XY: 74374

African (AFR) AF: 0.0371 AC: 1540 AN: 41522

American (AMR) AF: 0.0817 AC: 1250 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 433 AN: 3468

East Asian (EAS) AF: 0.0657 AC: 339 AN: 5158

South Asian (SAS) AF: 0.178 AC: 859 AN: 4826

European-Finnish (FIN) AF: 0.132 AC: 1398 AN: 10580

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10324 AN: 68000

Other (OTH) AF: 0.0947 AC: 200 AN: 2112

Alfa AF: 0.129 Hom.: 187

Bravo AF: 0.0984

Asia WGS AF: 0.134 AC: 467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.50
PhyloP100		-0.93
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: rs4135212; hg19: chr9-113008423;