9-110245009-T-G

Variant names:

• chr9-110245009-T-G
• rs4135220
• NM_003329.4:c.190-166A>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.190-166A>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
• Publications: 9 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=-0.88).
• 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 rank	MANE	Protein	UniProt
TXN	NM_003329.4	c.190-166A>C		intron_variant	Intron 3 of 4	ENST00000374517.6	NP_003320.2
TXN	NM_001244938.2	c.130-166A>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.190-166A>C		intron_variant	Intron 3 of 4	1	NM_003329.4	ENSP00000363641.5
TXN	ENST00000374515.9	c.130-166A>C		intron_variant	Intron 2 of 3	1		ENSP00000363639.5
TXN	ENST00000487892.1	n.108A>C		non_coding_transcript_exon_variant	Exon 1 of 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

African (AFR) AF: 0.695 AC: 7028 AN: 10118

American (AMR) AF: 0.722 AC: 10785 AN: 14928

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 5211 AN: 9770

East Asian (EAS) AF: 0.925 AC: 23250 AN: 25124

South Asian (SAS) AF: 0.632 AC: 19775 AN: 31292

European-Finnish (FIN) AF: 0.474 AC: 12239 AN: 25824

Middle Eastern (MID) AF: 0.596 AC: 1781 AN: 2986

European-Non Finnish (NFE) AF: 0.518 AC: 99535 AN: 192010

Other (OTH) AF: 0.574 AC: 10742 AN: 18706

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

African (AFR) AF: 0.695 AC: 28785 AN: 41438

American (AMR) AF: 0.680 AC: 10379 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1807 AN: 3472

East Asian (EAS) AF: 0.911 AC: 4716 AN: 5174

South Asian (SAS) AF: 0.629 AC: 3034 AN: 4824

European-Finnish (FIN) AF: 0.463 AC: 4866 AN: 10520

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34743 AN: 67958

Other (OTH) AF: 0.613 AC: 1295 AN: 2112

Alfa AF: 0.566 Hom.: 10365

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
PhyloP100		-0.14
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: rs4135220; hg19: chr9-113007289;