rs386833468
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The ENST00000340010.10(SLC26A3):c.177_178insC(p.Ile60HisfsTer11) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
SLC26A3
ENST00000340010.10 frameshift
ENST00000340010.10 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.154
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 Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 7-107793835-T-TG is Pathogenic according to our data. Variant chr7-107793835-T-TG is described in ClinVar as [Pathogenic]. Clinvar id is 55986.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC26A3 | NM_000111.3 | c.177_178insC | p.Ile60HisfsTer11 | frameshift_variant | 3/21 | ENST00000340010.10 | NP_000102.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC26A3 | ENST00000340010.10 | c.177_178insC | p.Ile60HisfsTer11 | frameshift_variant | 3/21 | 1 | NM_000111.3 | ENSP00000345873 | P1 | |
SLC26A3 | ENST00000453332.1 | c.177_178insC | p.Ile60HisfsTer11 | frameshift_variant | 3/4 | 4 | ENSP00000395955 | |||
SLC26A3 | ENST00000379083.7 | c.132-5_132-4insC | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant | 2 | ENSP00000368375 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251432Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135890
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461800Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727196
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Congenital secretory diarrhea, chloride type Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) | - | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 27, 2024 | This sequence change creates a premature translational stop signal (p.Ile60Hisfs*11) in the SLC26A3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC26A3 are known to be pathogenic (PMID: 9718329, 21394828). This variant is present in population databases (rs386833468, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with congenital chloride diarrhea (PMID: 9554749). ClinVar contains an entry for this variant (Variation ID: 55986). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
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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