Variant chr1-53910028-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.297

Variant links:

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]

DIO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
DIO1	NM_000792.7 linkuse as main transcript	c.*29C>T		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 linkuse as main transcript	c.*29C>T		3_prime_UTR_variant	4/4	1	NM_000792.7	ENSP00000354643	P1	P49895-1

Frequencies

GnomAD3 genomes

AF:

0.308

AC:

46799

AN:

151950

Hom.:

7756

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.350

AC XY:

252932

AN XY:

722374

show subpopulations

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.:

AF XY:

0.311

AC XY:

23143

AN XY:

74308

show subpopulations

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over