chr12-104283168-A-C

Variant names:

• chr12-104283168-A-C
• rs10861185
• NM_001093771.3:c.305-5763A>C

Variant summary

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

The NM_001093771.3(TXNRD1):​c.305-5763A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,034 control chromosomes in the GnomAD database, including 27,193 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 (27193 hom., cov: 32)
• Consequence: TXNRD1 NM_001093771.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 9 publications found

Genes affected

TXNRD1 (HGNC:12437): (thioredoxin reductase 1) The protein encoded by this gene belongs to the pyridine nucleotide-disulfide oxidoreductase family, and is a member of the thioredoxin (Trx) system. Three thioredoxin reductase (TrxR) isozymes are found in mammals. TrxRs are selenocysteine-containing flavoenzymes, which reduce thioredoxins, as well as other substrates, and play a key role in redox homoeostasis. This gene encodes an ubiquitously expressed, cytosolic form of TrxR, which functions as a homodimer containing FAD, and selenocysteine (Sec) at the active site. Sec is encoded by UGA codon that normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, the Sec insertion sequence (SECIS) element, which is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. Alternative splicing, primarily at the 5' end, results in transcript variants encoding same or different isoforms, including a glutaredoxin-containing isoform that is predominantly expressed in testis. [provided by RefSeq, May 2017]

ENSG00000304986 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001093771.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNRD1	NM_001093771.3	MANE Select	c.305-5763A>C		intron	N/A	NP_001087240.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNRD1	ENST00000525566.6	TSL:1 MANE Select	c.305-5763A>C		intron	N/A	ENSP00000434516.1
	TXNRD1	ENST00000526006.1	TSL:1	n.371+192A>C		intron	N/A
	ENSG00000304986	ENST00000807558.1		n.255-1060T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90377 AN: 151914 Hom.: 27172 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.595 AC: 90437 AN: 152034 Hom.: 27193 Cov.: 32 AF XY: 0.588 AC XY: 43667 AN XY: 74306

African (AFR) AF: 0.654 AC: 27137 AN: 41470

American (AMR) AF: 0.582 AC: 8881 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2069 AN: 3470

East Asian (EAS) AF: 0.642 AC: 3317 AN: 5164

South Asian (SAS) AF: 0.612 AC: 2946 AN: 4812

European-Finnish (FIN) AF: 0.433 AC: 4577 AN: 10576

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39480 AN: 67964

Other (OTH) AF: 0.611 AC: 1290 AN: 2110

Alfa AF: 0.597 Hom.: 33040

Bravo AF: 0.609

Asia WGS AF: 0.621 AC: 2159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.6
DANN	Benign	0.43
PhyloP100		-1.5
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: rs10861185; hg19: chr12-104676946;