rs386833490
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_000111.3(SLC26A3):c.915C>T(p.Tyr305=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000514 in 1,613,914 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000051 ( 0 hom. )
Consequence
SLC26A3
NM_000111.3 synonymous
NM_000111.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.618
Genes affected
SLC26A3 (HGNC:3018): (solute carrier family 26 member 3) The protein encoded by this gene is a transmembrane glycoprotein that transports chloride ions across the cell membrane in exchange for bicarbonate ions. It is localized to the mucosa of the lower intestinal tract, particularly to the apical membrane of columnar epithelium and some goblet cells. The protein is essential for intestinal chloride absorption, and mutations in this gene have been associated with congenital chloride diarrhea. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 7-107786883-G-A is Benign according to our data. Variant chr7-107786883-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 911074.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC26A3 | NM_000111.3 | c.915C>T | p.Tyr305= | synonymous_variant | 8/21 | ENST00000340010.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC26A3 | ENST00000340010.10 | c.915C>T | p.Tyr305= | synonymous_variant | 8/21 | 1 | NM_000111.3 | P1 | |
SLC26A3 | ENST00000468551.1 | n.193C>T | non_coding_transcript_exon_variant | 2/5 | 2 | ||||
SLC26A3 | ENST00000379083.7 | c.*706C>T | 3_prime_UTR_variant, NMD_transcript_variant | 8/20 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152158Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000597 AC: 15AN: 251248Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135804
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GnomAD4 exome AF: 0.0000506 AC: 74AN: 1461756Hom.: 0 Cov.: 31 AF XY: 0.0000550 AC XY: 40AN XY: 727190
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GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74330
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Congenital secretory diarrhea, chloride type Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
SLC26A3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 07, 2021 | 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). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: 26
Find out detailed SpliceAI scores and Pangolin per-transcript scores at