4-25655721-CGGCAGGTAGGCAGTGCCCCGGCGGCGGCTGCGGCAGGCGGTCCTGGAATGTGCGAGGGGCGTGATGACAGCGGCCAGCCTCTTTGCGCAACACCTTCGCCATATATACCCGGGGCGCTGCGCTCCACCTGGCCGCCGCCTCCAGCCCAGCACCTGCGGAGGGAGCGCTGGTGAGTACCGCCGCCGG-C

Position:

• chr4-25655721-CGGCAGGTAGGCAGTGCCCCGGCGGCGGCTGCGGCAGGCGGTCCTGGAATGTGCGAGGGGCGTGATGACAGCGGCCAGCCTCTTTGCGCAACACCTTCGCCATATATACCCGGGGCGCTGCGCTCCACCTGGCCGCCGCCTCCAGCCCAGCACCTGCGGAGGGAGCGCTGGTGAGTACCGCCGCCGG-C

Variant summary

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

The 4-25655721-CGGCAGGTAGGCAGTGCCCCGGCGGCGGCTGCGGCAGGCGGTCCTGGAATGTGCGAGGGGCGTGATGACAGCGGCCAGCCTCTTTGCGCAACACCTTCGCCATATATACCCGGGGCGCTGCGCTCCACCTGGCCGCCGCCTCCAGCCCAGCACCTGCGGAGGGAGCGCTGGTGAGTACCGCCGCCGG-C variant causes a splice donor, splice donor 5th base, 5 prime UTR, 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, splice_donor_5th_base, 5_prime_UTR, 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/exons	MANE	Protein	UniProt
SLC34A2	NM_006424.3			splice_donor_variant, splice_donor_5th_base_variant, 5_prime_UTR_variant, intron_variant	1/13	ENST00000382051.8	NP_006415.3
SLC34A2	NM_001177998.2			splice_donor_variant, splice_donor_5th_base_variant, 5_prime_UTR_variant, intron_variant	1/13		NP_001171469.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC34A2	ENST00000382051.8			splice_donor_variant, splice_donor_5th_base_variant, 5_prime_UTR_variant, intron_variant	1/13	1	NM_006424.3	ENSP00000371483	P4
SLC34A2	ENST00000504570.5			splice_donor_variant, splice_donor_5th_base_variant, 5_prime_UTR_variant, intron_variant	1/13	1		ENSP00000425501	A2
SLC34A2	ENST00000513204.5	c.-4+371_-4+556del		intron_variant		4		ENSP00000423038
SLC34A2	ENST00000645788.1	c.-3-6770_-3-6585del		intron_variant				ENSP00000494094	A2

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

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 01, 2006

- -

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;