chr4-25662803-AACCTACCCACTCT-A

Position:

• chr4-25662803-AACCTACCCACTCT-A

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_006424.3(SLC34A2):​c.212_224del​(p.Asn71IlefsTer27) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC34A2 NM_006424.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.48

Genes affected

SLC34A2 (HGNC:11020): (solute carrier family 34 member 2) The protein encoded by this gene is a pH-sensitive sodium-dependent phosphate transporter. Phosphate uptake is increased at lower pH. Defects in this gene are a cause of pulmonary alveolar microlithiasis. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Pathogenic. Variant got 11 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 4-25662803-AACCTACCCACTCT-A is Pathogenic according to our data. Variant chr4-25662803-AACCTACCCACTCT-A is described in ClinVar as [Pathogenic]. Clinvar id is 208162.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC34A2	NM_006424.3	c.212_224del	p.Asn71IlefsTer27	frameshift_variant	3/13	ENST00000382051.8	NP_006415.3
SLC34A2	NM_001177998.2	c.209_221del	p.Asn70IlefsTer27	frameshift_variant	3/13		NP_001171469.2
SLC34A2	NM_001177999.2	c.209_221del	p.Asn70IlefsTer27	frameshift_variant	3/13		NP_001171470.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC34A2	ENST00000382051.8	c.212_224del	p.Asn71IlefsTer27	frameshift_variant	3/13	1	NM_006424.3	ENSP00000371483	P4

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000756

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

PULMONARY ALVEOLAR MICROLITHIASIS Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

Medical Genetics UMG, Mater Domini University Hospital/ Magna Graecia University of Catanzaro

Apr 01, 2015

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs796065044; hg19: chr4-25664425;