rs267607067
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_003041.4(SLC5A2):c.500del(p.Gln167ArgfsTer20) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000651 in 1,613,870 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: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000064 ( 0 hom. )
Consequence
SLC5A2
NM_003041.4 frameshift
NM_003041.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.36
Genes affected
SLC5A2 (HGNC:11037): (solute carrier family 5 member 2) This gene encodes a member of the sodium glucose cotransporter family which are sodium-dependent glucose transport proteins. The encoded protein is the major cotransporter involved in glucose reabsorption in the kidney. Mutations in this gene are associated with renal glucosuria. Two transcript variants, one protein-coding and one not, have been found for this gene. [provided by RefSeq, Feb 2015]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 16 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant 16-31486200-CA-C is Pathogenic according to our data. Variant chr16-31486200-CA-C is described in ClinVar as [Pathogenic]. Clinvar id is 12906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC5A2 | NM_003041.4 | c.500del | p.Gln167ArgfsTer20 | frameshift_variant | 5/14 | ENST00000330498.4 | |
SLC5A2 | XM_006721072.5 | c.500del | p.Gln167ArgfsTer20 | frameshift_variant | 5/13 | ||
SLC5A2 | XM_024450402.2 | c.500del | p.Gln167ArgfsTer20 | frameshift_variant | 5/11 | ||
SLC5A2 | NR_130783.2 | n.514del | non_coding_transcript_exon_variant | 5/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC5A2 | ENST00000330498.4 | c.500del | p.Gln167ArgfsTer20 | frameshift_variant | 5/14 | 1 | NM_003041.4 | P1 | |
SLC5A2 | ENST00000419665.6 | c.500del | p.Gln167ArgfsTer20 | frameshift_variant, NMD_transcript_variant | 5/12 | 1 | |||
SLC5A2 | ENST00000569576.5 | c.371del | p.Gln124ArgfsTer20 | frameshift_variant | 5/5 | 4 | |||
SLC5A2 | ENST00000565446.1 | n.374del | non_coding_transcript_exon_variant | 3/3 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152108Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251452Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135908
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GnomAD4 exome AF: 0.0000643 AC: 94AN: 1461762Hom.: 0 Cov.: 31 AF XY: 0.0000591 AC XY: 43AN XY: 727180
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GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152108Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74292
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial renal glucosuria Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2004 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 04, 2021 | - - |
SLC5A2-related condition Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 11, 2023 | The SLC5A2 c.500delA variant is predicted to result in a frameshift and premature protein termination (p.Gln167Argfs*20). This variant has been reported in the compound heterozygous state in an individual with Renal glucosuria (Calado et al. 2004. PubMed ID: 14614622; Supplement, Hureaux et al. 2019. PubMed ID: 31672324). This variant is reported in 0.0040% of alleles in individuals of African descent in gnomAD. Frameshift variants in SLC5A2 are expected to be pathogenic. This variant is interpreted 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