rs11206244

Variant names:

• chr1-53910028-C-T
• rs11206244
• NM_000792.7:c.*29C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 46 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000792.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIO1	NM_000792.7	MANE Select	c.*29C>T		3_prime_UTR	Exon 4 of 4	NP_000783.2
	DIO1	NM_001039715.3		c.*29C>T		3_prime_UTR	Exon 3 of 3	NP_001034804.1	P49895-4
	DIO1	NM_213593.5		c.*29C>T		3_prime_UTR	Exon 4 of 4	NP_998758.1	P49895-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIO1	ENST00000361921.8	TSL:1 MANE Select	c.*29C>T		3_prime_UTR	Exon 4 of 4	ENSP00000354643.4	P49895-1
	DIO1	ENST00000322679.10	TSL:1	c.*93C>T		3_prime_UTR	Exon 3 of 3	ENSP00000323198.6	P49895-5
	DIO1	ENST00000525044.5	TSL:1	n.*221C>T		non_coding_transcript_exon	Exon 3 of 3	ENSP00000436550.1	E9PI35

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

GnomAD2 exomes AF: 0.362 AC: 90909 AN: 251062 AF XY: 0.363

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 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

African (AFR) AF: 0.190 AC: 6319 AN: 33232

American (AMR) AF: 0.547 AC: 24462 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 8782 AN: 26074

East Asian (EAS) AF: 0.142 AC: 5638 AN: 39610

South Asian (SAS) AF: 0.464 AC: 39945 AN: 86068

European-Finnish (FIN) AF: 0.339 AC: 18111 AN: 53374

Middle Eastern (MID) AF: 0.292 AC: 1677 AN: 5736

European-Non Finnish (NFE) AF: 0.343 AC: 378131 AN: 1101554

Other (OTH) AF: 0.331 AC: 19826 AN: 59946

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

African (AFR) AF: 0.202 AC: 8383 AN: 41506

American (AMR) AF: 0.451 AC: 6884 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1214 AN: 3470

East Asian (EAS) AF: 0.151 AC: 781 AN: 5180

South Asian (SAS) AF: 0.452 AC: 2179 AN: 4818

European-Finnish (FIN) AF: 0.334 AC: 3528 AN: 10548

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22909 AN: 67972

Other (OTH) AF: 0.304 AC: 640 AN: 2104

Alfa AF: 0.330 Hom.: 31550

Bravo AF: 0.307

Asia WGS AF: 0.288 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		0.30
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11206244;

hg19: chr1-54375701;

COSMIC: COSV59518151;

COSMIC: COSV59518151;