chr4-25662803-AACCTACCCACTCT-A

Variant names:

• chr4-25662803-AACCTACCCACTCT-A
• rs796065044
• NM_006424.3:c.212_224delACCTACCCACTCT

Variant summary

Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PVS1 PP5

The NM_006424.3(SLC34A2):​c.212_224delACCTACCCACTCT​(p.Asn71IlefsTer27) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 2 publications found

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]

SLC34A2 Gene-Disease associations (from GenCC):

• pulmonary alveolar microlithiasis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet

ACMG classification

Our verdict: Likely_pathogenic. The variant received 9 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant 4-25662803-AACCTACCCACTCT-A is Pathogenic according to our data. Variant chr4-25662803-AACCTACCCACTCT-A is described in ClinVar as Pathogenic. ClinVar VariationId is 208162.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006424.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC34A2	NM_006424.3	MANE Select	c.212_224delACCTACCCACTCT	p.Asn71IlefsTer27	frameshift	Exon 3 of 13	NP_006415.3	O95436-1
	SLC34A2	NM_001177998.2		c.209_221delACCTACCCACTCT	p.Asn70IlefsTer27	frameshift	Exon 3 of 13	NP_001171469.2	O95436-2
	SLC34A2	NM_001177999.2		c.209_221delACCTACCCACTCT	p.Asn70IlefsTer27	frameshift	Exon 3 of 13	NP_001171470.2	O95436-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC34A2	ENST00000382051.8	TSL:1 MANE Select	c.212_224delACCTACCCACTCT	p.Asn71IlefsTer27	frameshift	Exon 3 of 13	ENSP00000371483.3	O95436-1
	SLC34A2	ENST00000503434.5	TSL:1	c.209_221delACCTACCCACTCT	p.Asn70IlefsTer27	frameshift	Exon 3 of 13	ENSP00000423021.1	O95436-2
	SLC34A2	ENST00000504570.5	TSL:1	c.209_221delACCTACCCACTCT	p.Asn70IlefsTer27	frameshift	Exon 3 of 13	ENSP00000425501.1	O95436-2

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	PULMONARY ALVEOLAR MICROLITHIASIS (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.5
Mutation Taster		=2/198	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs796065044; hg19: chr4-25664425;