rs386833485
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1_ModeratePM2PP5_Very_Strong
The ENST00000340010.10(SLC26A3):c.571-1G>T variant causes a splice acceptor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,612,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Consequence
ENST00000340010.10 splice_acceptor
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC26A3 | NM_000111.3 | c.571-1G>T | splice_acceptor_variant | ENST00000340010.10 | NP_000102.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC26A3 | ENST00000340010.10 | c.571-1G>T | splice_acceptor_variant | 1 | NM_000111.3 | ENSP00000345873 | P1 | |||
SLC26A3 | ENST00000379083.7 | c.*362-1G>T | splice_acceptor_variant, NMD_transcript_variant | 2 | ENSP00000368375 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152092Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000807 AC: 2AN: 247846Hom.: 0 AF XY: 0.00000747 AC XY: 1AN XY: 133894
GnomAD4 exome AF: 0.0000370 AC: 54AN: 1460364Hom.: 0 Cov.: 32 AF XY: 0.0000358 AC XY: 26AN XY: 726288
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152092Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74298
ClinVar
Submissions by phenotype
Congenital secretory diarrhea, chloride type Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Genetics and Molecular Pathology, SA Pathology | Jul 05, 2022 | - - |
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 | Jul 10, 2023 | This sequence change affects an acceptor splice site in intron 5 of the SLC26A3 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SLC26A3 are known to be pathogenic (PMID: 9718329, 21394828). This variant is present in population databases (rs386833485, gnomAD 0.002%). Disruption of this splice site has been observed in individuals with congenital chloride diarrhea (PMID: 9718329). This variant is also known as IVS5-1G>T. ClinVar contains an entry for this variant (Variation ID: 56004). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at