chrX-74421523-A-AGGCAGC
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_006517.5(SLC16A2):c.-102_-97dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 984,326 control chromosomes in the GnomAD database, including 46 homozygotes. There are 478 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.010 ( 24 hom., 260 hem., cov: 22)
Exomes 𝑓: 0.0012 ( 22 hom. 218 hem. )
Consequence
SLC16A2
NM_006517.5 5_prime_UTR
NM_006517.5 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.19
Genes affected
SLC16A2 (HGNC:10923): (solute carrier family 16 member 2) This gene encodes an integral membrane protein that functions as a transporter of thyroid hormone. The encoded protein facilitates the cellular importation of thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and diidothyronine (T2). This gene is expressed in many tissues and likely plays an important role in the development of the central nervous system. Loss of function mutations in this gene are associated with psychomotor retardation in males while females exhibit no neurological defects and more moderate thyroid-deficient phenotypes. This gene is subject to X-chromosome inactivation. Mutations in this gene are the cause of Allan-Herndon-Dudley syndrome. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant X-74421523-A-AGGCAGC is Benign according to our data. Variant chrX-74421523-A-AGGCAGC is described in ClinVar as [Likely_benign]. Clinvar id is 587847.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1167/111225) while in subpopulation AFR AF= 0.0364 (1111/30521). AF 95% confidence interval is 0.0346. There are 24 homozygotes in gnomad4. There are 260 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 24 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC16A2 | NM_006517.5 | c.-102_-97dup | 5_prime_UTR_variant | 1/6 | ENST00000587091.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC16A2 | ENST00000587091.6 | c.-102_-97dup | 5_prime_UTR_variant | 1/6 | 1 | NM_006517.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0105 AC: 1163AN: 111179Hom.: 24 Cov.: 22 AF XY: 0.00774 AC XY: 259AN XY: 33451
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GnomAD3 exomes AF: 0.00249 AC: 296AN: 118869Hom.: 5 AF XY: 0.00147 AC XY: 56AN XY: 38041
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GnomAD4 exome AF: 0.00117 AC: 1020AN: 873101Hom.: 22 Cov.: 16 AF XY: 0.000894 AC XY: 218AN XY: 243865
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GnomAD4 genome AF: 0.0105 AC: 1167AN: 111225Hom.: 24 Cov.: 22 AF XY: 0.00776 AC XY: 260AN XY: 33507
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 23, 2022 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 31, 2019 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 07, 2020 | - - |
Allan-Herndon-Dudley syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 06, 2021 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at