chr1-53894498-G-A
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_000792.7(DIO1):c.288G>A(p.Pro96=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,614,150 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0087 ( 17 hom., cov: 33)
Exomes 𝑓: 0.00082 ( 20 hom. )
Consequence
DIO1
NM_000792.7 synonymous
NM_000792.7 synonymous
Scores
7
Clinical Significance
Conservation
PhyloP100: -6.37
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.00208956).
BP6
?
Variant 1-53894498-G-A is Benign according to our data. Variant chr1-53894498-G-A is described in ClinVar as [Benign]. Clinvar id is 708355.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-6.37 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00875 (1332/152268) while in subpopulation AFR AF= 0.0311 (1290/41540). AF 95% confidence interval is 0.0296. There are 17 homozygotes in gnomad4. There are 612 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1324 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DIO1 | NM_000792.7 | c.288G>A | p.Pro96= | synonymous_variant | 1/4 | ENST00000361921.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DIO1 | ENST00000361921.8 | c.288G>A | p.Pro96= | synonymous_variant | 1/4 | 1 | NM_000792.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00870 AC: 1324AN: 152150Hom.: 17 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.00214 AC: 532AN: 248944Hom.: 9 AF XY: 0.00137 AC XY: 184AN XY: 134786
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GnomAD4 exome AF: 0.000822 AC: 1202AN: 1461882Hom.: 20 Cov.: 31 AF XY: 0.000755 AC XY: 549AN XY: 727246
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GnomAD4 genome ? AF: 0.00875 AC: 1332AN: 152268Hom.: 17 Cov.: 33 AF XY: 0.00822 AC XY: 612AN XY: 74452
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Asia WGS
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Mar 29, 2018 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
Vest4
MVP
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at