rs12095080

Positions:

• chr1-53911057-A-G

Variant summary

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

The NM_000792.7(DIO1):​c.*1058A>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.113 in 152,748 control chromosomes in the GnomAD database, including 1,144 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 0.11 (1139 hom., cov: 33)
  • Exomes 𝑓: 0.12 (5 hom.)
• Consequence: DIO1 NM_000792.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.89

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=-0.62).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIO1	NM_000792.7	c.*1058A>G		3_prime_UTR_variant	4/4	ENST00000361921.8	NP_000783.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIO1	ENST00000361921.8	c.*1058A>G		3_prime_UTR_variant	4/4	1	NM_000792.7	ENSP00000354643	P1
DIO1	ENST00000322679.10	c.*1122A>G		3_prime_UTR_variant	3/3	1		ENSP00000323198

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17161 AN: 152198 Hom.: 1142 Cov.: 33

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0842

Gnomad ASJ AF: 0.0806

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0418

Gnomad FIN AF: 0.0815

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0992

Gnomad OTH AF: 0.115

GnomAD4 exome AF: 0.120 AC: 52 AN: 432 Hom.: 5 Cov.: 0 AF XY: 0.123 AC XY: 32 AN XY: 260

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.113 AC: 17165 AN: 152316 Hom.: 1139 Cov.: 33 AF XY: 0.111 AC XY: 8238 AN XY: 74482

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.0839

Gnomad4 ASJ AF: 0.0806

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0418

Gnomad4 FIN AF: 0.0815

Gnomad4 NFE AF: 0.0992

Gnomad4 OTH AF: 0.114

Alfa AF: 0.106 Hom.: 873

Bravo AF: 0.117

Asia WGS AF: 0.0300 AC: 105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.85

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: rs12095080; hg19: chr1-54376730; COSMIC: COSV59517644; COSMIC: COSV59517644;