rs11206244

chr1-53910028-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000792.7(DIO1):c.*29C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 1,602,354 control chromosomes in the GnomAD database, including 98,183 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 0.31 (7764 hom., cov: 32)
  • Exomes 𝑓: 0.35 (90419 hom.)
• Consequence: DIO1 NM_000792.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297

Genes affected

DIO1 (HGNC:2883): (iodothyronine deiodinase 1) The protein encoded by this gene belongs to the iodothyronine deiodinase family. It catalyzes the activation, as well as the inactivation of thyroid hormone by outer and inner ring deiodination, respectively. The activation reaction involves the conversion of the prohormone thyroxine (3,5,3',5'-tetraiodothyronine, T4), secreted by the thyroid gland, to the bioactive thyroid hormone (3,5,3'-triiodothyronine, T3) by 5'-deiodination. This protein provides most of the circulating T3, which is essential for growth, differentiation and basal metabolism in vertebrates. This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec) at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2018]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIO1	NM_000792.7	c.*29C>T		3_prime_UTR_variant	4/4	ENST00000361921.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIO1	ENST00000361921.8	c.*29C>T		3_prime_UTR_variant	4/4	1	NM_000792.7	P1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46799 AN: 151950 Hom.: 7756 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.305

GnomAD3 exomes AF: 0.362 AC: 90909 AN: 251062 Hom.: 18205 AF XY: 0.363 AC XY: 49227 AN XY: 135704

Gnomad AFR exome AF: 0.200

Gnomad AMR exome AF: 0.566

Gnomad ASJ exome AF: 0.337

Gnomad EAS exome AF: 0.151

Gnomad SAS exome AF: 0.466

Gnomad FIN exome AF: 0.332

Gnomad NFE exome AF: 0.338

Gnomad OTH exome AF: 0.360

GnomAD4 exome AF: 0.347 AC: 502891 AN: 1450284 Hom.: 90419 Cov.: 27 AF XY: 0.350 AC XY: 252932 AN XY: 722374

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.547

Gnomad4 ASJ exome AF: 0.337

Gnomad4 EAS exome AF: 0.142

Gnomad4 SAS exome AF: 0.464

Gnomad4 FIN exome AF: 0.339

Gnomad4 NFE exome AF: 0.343

Gnomad4 OTH exome AF: 0.331

GnomAD4 genome AF: 0.308 AC: 46829 AN: 152070 Hom.: 7764 Cov.: 32 AF XY: 0.311 AC XY: 23143 AN XY: 74308

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.304

Alfa AF: 0.337 Hom.: 14347

Bravo AF: 0.307

Asia WGS AF: 0.288 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	11
Dann	Benign	0.82

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

LitVar

Other links and lift over

dbSNP: rs11206244; hg19: chr1-54375701; COSMIC: COSV59518151; COSMIC: COSV59518151;