rs121918610

chr5-177386019-GC-TT

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PS1_Moderate PP5

The NM_003052.5(SLC34A1):c.142_143delinsTT(p.Ala48Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 NM_003052.5 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 3 ACMG points.

• PS1: Transcript NM_003052.5 (SLC34A1) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt
• 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	UniProt
SLC34A1	NM_003052.5	c.142_143delinsTT	p.Ala48Phe	missense_variant	3/13	ENST00000324417.6
SLC34A1	NM_001167579.2	c.142_143delinsTT	p.Ala48Phe	missense_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC34A1	ENST00000324417.6	c.142_143delinsTT	p.Ala48Phe	missense_variant	3/13	1	NM_003052.5	P1
SLC34A1	ENST00000504577.5	c.142_143delinsTT	p.Ala48Phe	missense_variant	3/4	4
SLC34A1	ENST00000512593.5	c.142_143delinsTT	p.Ala48Phe	missense_variant	3/9	2
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

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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: rs121918610; hg19: chr5-176813020;