chr7-107793742-C-CTT
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000111.3(SLC26A3):c.269_270dupAA(p.Gly91LysfsTer3) variant causes a frameshift, splice region change. The variant allele was found at a frequency of 0.00000372 in 1,612,550 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
Consequence
NM_000111.3 frameshift, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC26A3 | ENST00000340010.10 | c.269_270dupAA | p.Gly91LysfsTer3 | frameshift_variant, splice_region_variant | Exon 3 of 21 | 1 | NM_000111.3 | ENSP00000345873.5 | ||
SLC26A3 | ENST00000453332.1 | c.269_270dupAA | p.Gly91LysfsTer3 | frameshift_variant, splice_region_variant | Exon 3 of 4 | 4 | ENSP00000395955.1 | |||
SLC26A3 | ENST00000379083.7 | n.*60_*61dupAA | splice_region_variant, non_coding_transcript_exon_variant | Exon 3 of 20 | 2 | ENSP00000368375.3 | ||||
SLC26A3 | ENST00000379083.7 | n.*60_*61dupAA | 3_prime_UTR_variant | Exon 3 of 20 | 2 | ENSP00000368375.3 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152046Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250454Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135414
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460504Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726502
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152046Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74286
ClinVar
Submissions by phenotype
Congenital secretory diarrhea, chloride type Pathogenic:2
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not provided Pathogenic:1
For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Gly91Lysfs*3) 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 (rs386833476, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with clinical features of congenital chloride diarrhea (PMID: 9718329, 31680349, 33191723, 34503561). This variant is also known as c.268–269insAA. ClinVar contains an entry for this variant (Variation ID: 55994). -
Polyhydramnios;C0020305:Hydrops fetalis;C0021843:Intestinal obstruction Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at