6-150369100-C-G
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_203395.3(IYD):āc.69C>Gā(p.Ala23=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,613,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00056 ( 0 hom., cov: 31)
Exomes š: 0.000081 ( 0 hom. )
Consequence
IYD
NM_203395.3 synonymous
NM_203395.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.25
Genes affected
IYD (HGNC:21071): (iodotyrosine deiodinase) This gene encodes an enzyme that catalyzes the oxidative NADPH-dependent deiodination of mono- and diiodotyrosine, which are the halogenated byproducts of thyroid hormone production. The N-terminus of the protein functions as a membrane anchor. Mutations in this gene cause congenital hypothyroidism due to dyshormonogenesis type 4, which is also referred to as deiodinase deficiency, or iodotyrosine dehalogenase deficiency, or thyroid hormonogenesis type 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
Variant 6-150369100-C-G is Benign according to our data. Variant chr6-150369100-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 709827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-150369100-C-G is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-2.25 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IYD | NM_203395.3 | c.69C>G | p.Ala23= | synonymous_variant | 1/5 | ENST00000344419.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IYD | ENST00000344419.8 | c.69C>G | p.Ala23= | synonymous_variant | 1/5 | 1 | NM_203395.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000560 AC: 85AN: 151742Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000131 AC: 33AN: 251222Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135754
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GnomAD4 exome AF: 0.0000814 AC: 119AN: 1461864Hom.: 0 Cov.: 31 AF XY: 0.0000674 AC XY: 49AN XY: 727236
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GnomAD4 genome AF: 0.000560 AC: 85AN: 151860Hom.: 0 Cov.: 31 AF XY: 0.000593 AC XY: 44AN XY: 74218
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
IYD-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 01, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 21, 2017 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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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