rs794729658

Positions:

• chr9-137233920-GC-G

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001177316.2(SLC34A3):​c.908delC​(p.Pro303fs) 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
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• 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]

ACMG classification

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	Protein	UniProt
SLC34A3	NM_001177316.2	c.908delC	p.Pro303fs	frameshift_variant	9/13	ENST00000673835.1	NP_001170787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC34A3	ENST00000673835.1	c.908delC	p.Pro303fs	frameshift_variant	9/13		NM_001177316.2	ENSP00000501114.1
SLC34A3	ENST00000361134.2	c.908delC	p.Pro303fs	frameshift_variant	9/13	2		ENSP00000355353.2
SLC34A3	ENST00000538474.5	c.908delC	p.Pro303fs	frameshift_variant	9/13	5		ENSP00000442397.1
SLC34A3	ENST00000673865.1	c.908delC	p.Pro303fs	frameshift_variant	9/10			ENSP00000501101.1

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151606 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD4 exome Cov.: 37

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151606 Hom.: 0 Cov.: 27 AF XY: 0.0000135 AC XY: 1 AN XY: 74006

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.0000712 Hom.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

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

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs794729658; hg19: chr9-140128372;