4-25655721-CGGCAGGTAGGCAGTGCCCCGGCGGCGGCTGCGGCAGGCGGTCCTGGAATGTGCGAGGGGCGTGATGACAGCGGCCAGCCTCTTTGCGCAACACCTTCGCCATATATACCCGGGGCGCTGCGCTCCACCTGGCCGCCGCCTCCAGCCCAGCACCTGCGGAGGGAGCGCTGGTGAGTACCGCCGCCGG-C

Variant names:

• chr4-25655721-CGGCAGGTAGGCAGTGCCCCGGCGGCGGCTGCGGCAGGCGGTCCTGGAATGTGCGAGGGGCGTGATGACAGCGGCCAGCCTCTTTGCGCAACACCTTCGCCATATATACCCGGGGCGCTGCGCTCCACCTGGCCGCCGCCTCCAGCCCAGCACCTGCGGAGGGAGCGCTGGTGAGTACCGCCGCCGG-C
• NM_006424.3:c.-172_-4+17del

Variant summary

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

The NM_006424.3(SLC34A2):​c.-172_-4+17del variant causes a splice donor, 5 prime UTR truncation, exon loss, splice region, intron change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC34A2 NM_006424.3 splice_donor, 5_prime_UTR_truncation, exon_loss, splice_region, intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.24

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: Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease,
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 4-25655721-CGGCAGGTAGGCAGTGCCCCGGCGGCGGCTGCGGCAGGCGGTCCTGGAATGTGCGAGGGGCGTGATGACAGCGGCCAGCCTCTTTGCGCAACACCTTCGCCATATATACCCGGGGCGCTGCGCTCCACCTGGCCGCCGCCTCCAGCCCAGCACCTGCGGAGGGAGCGCTGGTGAGTACCGCCGCCGG-C is Pathogenic according to our data. Variant chr4-25655721-CGGCAGGTAGGCAGTGCCCCGGCGGCGGCTGCGGCAGGCGGTCCTGGAATGTGCGAGGGGCGTGATGACAGCGGCCAGCCTCTTTGCGCAACACCTTCGCCATATATACCCGGGGCGCTGCGCTCCACCTGGCCGCCGCCTCCAGCCCAGCACCTGCGGAGGGAGCGCTGGTGAGTACCGCCGCCGG-C is described in ClinVar as [Pathogenic]. Clinvar id is 5714.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC34A2	NM_006424.3	c.-172_-4+17del		splice_region_variant	Exon 1 of 13	ENST00000382051.8	NP_006415.3
SLC34A2	NM_006424.3	c.-172_-4+17del		splice_donor_variant, 5_prime_UTR_truncation, exon_loss_variant, splice_region_variant, intron_variant	Exon 1 of 13	ENST00000382051.8	NP_006415.3
SLC34A2	NM_006424.3	c.-172_-4+17del		non_coding_transcript_variant		ENST00000382051.8	NP_006415.3
SLC34A2	NM_006424.3	c.-172_-4+17del		upstream_gene_variant		ENST00000382051.8	NP_006415.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC34A2	ENST00000382051.8	c.-172_-4+17del		splice_region_variant	Exon 1 of 13	1	NM_006424.3	ENSP00000371483.3
SLC34A2	ENST00000382051	c.-172_-4+17del		splice_donor_variant, 5_prime_UTR_truncation, exon_loss_variant, splice_region_variant, intron_variant	Exon 1 of 13	1	NM_006424.3	ENSP00000371483.3
SLC34A2	ENST00000382051.8	c.-172_-4+17del		non_coding_transcript_variant		1	NM_006424.3	ENSP00000371483.3
SLC34A2	ENST00000382051.8	c.-172_-4+17del		upstream_gene_variant		1	NM_006424.3	ENSP00000371483.3

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

PULMONARY ALVEOLAR MICROLITHIASIS Pathogenic:1

Oct 01, 2006

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-25657343;