9-110246966-A-G

Variant names:

• chr9-110246966-A-G
• rs4135208
• NM_003329.4:c.190-2123T>C

Variant summary

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

The NM_003329.4(TXN):​c.190-2123T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,004 control chromosomes in the GnomAD database, including 6,352 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 0.29 (6352 hom., cov: 31)
• Consequence: TXN NM_003329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.333

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 (AMR) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXN	NM_003329.4	c.190-2123T>C		intron_variant	Intron 3 of 4	ENST00000374517.6	NP_003320.2
TXN	NM_001244938.2	c.130-2123T>C		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.190-2123T>C		intron_variant	Intron 3 of 4	1	NM_003329.4	ENSP00000363641.5
TXN	ENST00000374515.9	c.130-2123T>C		intron_variant	Intron 2 of 3	1		ENSP00000363639.5

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43459 AN: 151886 Hom.: 6353 Cov.: 31

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.286 AC: 43468 AN: 152004 Hom.: 6352 Cov.: 31 AF XY: 0.282 AC XY: 20962 AN XY: 74290

African (AFR) AF: 0.227 AC: 9424 AN: 41460

American (AMR) AF: 0.324 AC: 4941 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1157 AN: 3470

East Asian (EAS) AF: 0.302 AC: 1558 AN: 5164

South Asian (SAS) AF: 0.297 AC: 1429 AN: 4810

European-Finnish (FIN) AF: 0.218 AC: 2306 AN: 10566

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21676 AN: 67956

Other (OTH) AF: 0.333 AC: 703 AN: 2112

Alfa AF: 0.318 Hom.: 21309

Bravo AF: 0.291

Asia WGS AF: 0.293 AC: 1018 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	4.7
DANN	Benign	0.79
PhyloP100		-0.33
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

Publications

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Other links and lift over

dbSNP: rs4135208; hg19: chr9-113009246;