rs121918610

Positions:

• chr5-177386019-GC-TT

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PS1_Moderate PM2 PP5

The ENST00000324417.6(SLC34A1):​c.142_143delinsTT​(p.Ala48Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC34A1 ENST00000324417.6 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.893

Genes affected

SLC34A1 (HGNC:11019): (solute carrier family 34 member 1) Enables sodium:phosphate symporter activity. Involved in several processes, including phosphate ion homeostasis; phosphate ion transport; and response to lead ion. Located in several cellular components, including apical plasma membrane; mitotic spindle; and nuclear speck. Implicated in several diseases, including Fanconi syndrome (multiple); chronic kidney disease; hereditary hypophosphatemic rickets with hypercalciuria; hypophosphatemic nephrolithiasis/osteoporosis 1; and nephrolithiasis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PS1: Transcript ENST00000324417.6 (SLC34A1) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 5-177386019-GC-TT is Pathogenic according to our data. Variant chr5-177386019-GC-TT is described in ClinVar as [Pathogenic]. Clinvar id is 12931.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC34A1	NM_003052.5	c.142_143delinsTT	p.Ala48Phe	missense_variant	3/13	ENST00000324417.6	NP_003043.3
SLC34A1	NM_001167579.2	c.142_143delinsTT	p.Ala48Phe	missense_variant	3/9		NP_001161051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC34A1	ENST00000324417.6	c.142_143delinsTT	p.Ala48Phe	missense_variant	3/13	1	NM_003052.5	ENSP00000321424	P1
SLC34A1	ENST00000504577.5	c.142_143delinsTT	p.Ala48Phe	missense_variant	3/4	4		ENSP00000423733
SLC34A1	ENST00000512593.5	c.142_143delinsTT	p.Ala48Phe	missense_variant	3/9	2		ENSP00000423022
SLC34A1	ENST00000507685.5	n.226_227delinsTT		non_coding_transcript_exon_variant	3/10	2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hypophosphatemic nephrolithiasis/osteoporosis 1 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 26, 2002

- -

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: rs121918610; hg19: chr5-176813020;