NM_003052.5(SLC34A1):c.458G>T (p.Gly153Val) AND not provided

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Dec 15, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003233505.2

Allele description [Variation Report for NM_003052.5(SLC34A1):c.458G>T (p.Gly153Val)]

NM_003052.5(SLC34A1):c.458G>T (p.Gly153Val)

Gene:

SLC34A1:solute carrier family 34 member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q35.3

Genomic location:

Preferred name:

NM_003052.5(SLC34A1):c.458G>T (p.Gly153Val)

HGVS:

NC_000005.10:g.177386492G>T
NG_016223.1:g.7062G>T
NM_001167579.2:c.458G>T
NM_003052.5:c.458G>TMANE SELECT
NP_001161051.1:p.Gly153Val
NP_003043.3:p.Gly153Val
NC_000005.9:g.176813493G>T
NM_003052.4:c.458G>T

Protein change:

G153V; GLY153VAL

Links:

OMIM: 182309.0005; dbSNP: rs769409705

NCBI 1000 Genomes Browser:

rs769409705

Molecular consequence:

NM_001167579.2:c.458G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003052.5:c.458G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003931018	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Dec 7, 2022)	germline	clinical testing	Citation Link,
SCV004293235	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Dec 15, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26047794, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003931018

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Dec 7, 2022)

germline

clinical testing

Citation Link,

SCV004293235

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Dec 15, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile Hypercalcemia.

Schlingmann KP, Ruminska J, Kaufmann M, Dursun I, Patti M, Kranz B, Pronicka E, Ciara E, Akcay T, Bulus D, Cornelissen EA, Gawlik A, Sikora P, Patzer L, Galiano M, Boyadzhiev V, Dumic M, Vivante A, Kleta R, Dekel B, Levtchenko E, Bindels RJ, et al.

J Am Soc Nephrol. 2016 Feb;27(2):604-14. doi: 10.1681/ASN.2014101025. Epub 2015 Jun 5.

PubMed [citation]

PMID:: 26047794
PMCID:: PMC4731111

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From GeneDx, SCV003931018.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Published functional studies demonstrate G153V results in loss of function compared to wildtype (Schlingmann et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31589614, 26787776, 31188746, 33326653, 26047794)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV004293235.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 153 of the SLC34A1 protein (p.Gly153Val). This variant is present in population databases (rs769409705, gnomAD 0.004%). This missense change has been observed in individuals with infantile hypercalcemia (PMID: 26047794). ClinVar contains an entry for this variant (Variation ID: 234927). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SLC34A1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects SLC34A1 function (PMID: 26047794). This variant disrupts the p.Gly153 amino acid residue in SLC34A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26047794). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 12, 2024

ClinVar

Relating variation to medicine