rs182064161
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000453.3(SLC5A5):c.839+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0089 in 1,614,146 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0067 ( 10 hom., cov: 32)
Exomes 𝑓: 0.0091 ( 89 hom. )
Consequence
SLC5A5
NM_000453.3 intron
NM_000453.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.38
Genes affected
SLC5A5 (HGNC:11040): (solute carrier family 5 member 5) This gene encodes a member of the sodium glucose cotransporter family. The encoded protein is responsible for the uptake of iodine in tissues such as the thyroid and lactating breast tissue. The iodine taken up by the thyroid is incorporated into the metabolic regulators triiodothyronine (T3) and tetraiodothyronine (T4). Mutations in this gene are associated with thyroid dyshormonogenesis 1.[provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 19-17877874-C-T is Benign according to our data. Variant chr19-17877874-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 256200.We mark this variant Likely_benign, oryginal submissions are: {Benign=3, Uncertain_significance=1}. Variant chr19-17877874-C-T is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00674 (1026/152294) while in subpopulation EAS AF= 0.0206 (107/5192). AF 95% confidence interval is 0.0174. There are 10 homozygotes in gnomad4. There are 546 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 10 AR gene
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| SLC5A5 | NM_000453.3 | c.839+11C>T | intron_variant | ENST00000222248.4 | NP_000444.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| SLC5A5 | ENST00000222248.4 | c.839+11C>T | intron_variant | 1 | NM_000453.3 | ENSP00000222248 | P1 |
Frequencies
GnomAD3 genomes 0.00675 AC: 1027AN: 152176Hom.: 10 Cov.: 32
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GnomAD3 exomes AF: 0.00811 AC: 2038AN: 251366Hom.: 15 AF XY: 0.00824 AC XY: 1120AN XY: 135870
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GnomAD4 exome AF: 0.00913 AC: 13345AN: 1461852Hom.: 89 Cov.: 32 AF XY: 0.00898 AC XY: 6534AN XY: 727230
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GnomAD4 genome 0.00674 AC: 1026AN: 152294Hom.: 10 Cov.: 32 AF XY: 0.00733 AC XY: 546AN XY: 74468
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Thyroid dyshormonogenesis 1 Uncertain:1Benign:1
| Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
| Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
| Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at