dbSNP rs12095080: DIO1:c.*1058A>G (chr1-53911057-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.89

Publications

18 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DIO1	NM_000792.7	MANE Select	c.*1058A>G	3_prime_UTR	Exon 4 of 4	NP_000783.2
DIO1	NM_001039715.3		c.*1058A>G	3_prime_UTR	Exon 3 of 3	NP_001034804.1	P49895-4
DIO1	NM_213593.5		c.*1058A>G	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.*1058A>G		3_prime_UTR	Exon 4 of 4	ENSP00000354643.4	P49895-1
	DIO1	ENST00000322679.10	TSL:1	c.*1122A>G		3_prime_UTR	Exon 3 of 3	ENSP00000323198.6	P49895-5

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17161

AN:

152198

Hom.:

1142

Cov.:

show subpopulations

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:

AN:

432

Hom.:

Cov.:

AF XY:

0.123

AC XY:

AN XY:

260

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.120

AC:

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.113

AC:

17165

AN:

152316

Hom.:

1139

Cov.:

AF XY:

0.111

AC XY:

8238

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.178

AC:

7387

AN:

41556

American (AMR)

AF:

0.0839

AC:

1284

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0806

AC:

280

AN:

3472

East Asian (EAS)

AF:

0.000385

AC:

AN:

5192

South Asian (SAS)

AF:

0.0418

AC:

202

AN:

4830

European-Finnish (FIN)

AF:

0.0815

AC:

865

AN:

10616

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0992

AC:

6750

AN:

68026

Other (OTH)

AF:

0.114

AC:

242

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

781

1562

2344

3125

3906

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

352

528

704

880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.107

Hom.:

1188

Bravo

AF:

0.117

Asia WGS

AF:

0.0300

AC:

105

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

3.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over