rs794729658
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001177316.2(SLC34A3):c.908del(p.Pro303ArgfsTer40) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 151,606 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 0.0000066 ( 0 hom., cov: 27)
Consequence
SLC34A3
NM_001177316.2 frameshift
NM_001177316.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.199
Genes affected
SLC34A3 (HGNC:20305): (solute carrier family 34 member 3) This gene encodes a member of SLC34A transporter family of proteins, and is expressed primarily in the kidney. It is involved in transporting phosphate into cells via sodium cotransport in the renal brush border membrane, and contributes to the maintenance of inorganic phosphate concentration in the kidney. Mutations in this gene are associated with hereditary hypophosphatemic rickets with hypercalciuria. Alternatively spliced transcript variants varying in the 5' UTR have been found for this gene.[provided by RefSeq, Apr 2010]
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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 9-137233920-GC-G is Pathogenic according to our data. Variant chr9-137233920-GC-G is described in ClinVar as [Pathogenic]. Clinvar id is 1426.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC34A3 | NM_001177316.2 | c.908del | p.Pro303ArgfsTer40 | frameshift_variant | 9/13 | ENST00000673835.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC34A3 | ENST00000673835.1 | c.908del | p.Pro303ArgfsTer40 | frameshift_variant | 9/13 | NM_001177316.2 | P1 | ||
SLC34A3 | ENST00000361134.2 | c.908del | p.Pro303ArgfsTer40 | frameshift_variant | 9/13 | 2 | P1 | ||
SLC34A3 | ENST00000538474.5 | c.908del | p.Pro303ArgfsTer40 | frameshift_variant | 9/13 | 5 | P1 | ||
SLC34A3 | ENST00000673865.1 | c.908del | p.Pro303ArgfsTer40 | frameshift_variant | 9/10 |
Frequencies
GnomAD3 genomes ? AF: 0.00000660 AC: 1AN: 151606Hom.: 0 Cov.: 27
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GnomAD4 exome Cov.: 37
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GnomAD4 genome ? AF: 0.00000660 AC: 1AN: 151606Hom.: 0 Cov.: 27 AF XY: 0.0000135 AC XY: 1AN XY: 74006
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive hypophosphatemic bone disease Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München | Sep 30, 2017 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2006 | - - |
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