chr9-110244957-G-T

Variant names:

• chr9-110244957-G-T
• rs4135221
• NM_003329.4:c.190-114C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003329.4(TXN):​c.190-114C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000746 in 536,190 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: TXN NM_003329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.838
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXN	NM_003329.4	c.190-114C>A		intron_variant	Intron 3 of 4	ENST00000374517.6	NP_003320.2
TXN	NM_001244938.2	c.130-114C>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.190-114C>A		intron_variant	Intron 3 of 4	1	NM_003329.4	ENSP00000363641.5
TXN	ENST00000374515.9	c.130-114C>A		intron_variant	Intron 2 of 3	1		ENSP00000363639.5
TXN	ENST00000487892.1	n.160C>A		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000746 AC: 4 AN: 536190 Hom.: 0 Cov.: 7 AF XY: 0.00000350 AC XY: 1 AN XY: 286084

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 14856

American (AMR) AF: 0.0000724 AC: 2 AN: 27628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15048

East Asian (EAS) AF: 0.00 AC: 0 AN: 31942

South Asian (SAS) AF: 0.00 AC: 0 AN: 47220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3592

European-Non Finnish (NFE) AF: 0.00000613 AC: 2 AN: 326034

Other (OTH) AF: 0.00 AC: 0 AN: 26668

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.052379), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.5
DANN	Benign	0.61
PhyloP100		0.84

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: rs4135221; hg19: chr9-113007237;