rs121918610

Variant names:

• chr5-177386019-GC-TT
• rs121918610
• NM_003052.5:c.142_143delGCinsTT

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP5

The NM_003052.5(SLC34A1):​c.142_143delGCinsTT​(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. The variant is present in control chromosomes in GnomAd MNV project. The variant allele was found at a frequency of 0.00000403 in 1 alleles, including 0 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type MNV, 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).

• Frequency: GnomAD MNV: 𝑓 0.0000040 Genomes: not found (cov: 32)
• Consequence: SLC34A1 NM_003052.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.893
• Publications: 10 publications found

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]

SLC34A1 Gene-Disease associations (from GenCC):

• hypercalcemia, infantile, 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• dominant hypophosphatemia with nephrolithiasis or osteoporosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• primary Fanconi syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive infantile hypercalcemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hypophosphatemic nephrolithiasis/osteoporosis 1

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• Fanconi renotubular syndrome 2

  Inheritance: AR Classification: LIMITED, NO_KNOWN Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP5: Variant 5-177386019-GC-TT is Pathogenic according to our data. Variant chr5-177386019-GC-TT is described in ClinVar as Pathogenic. ClinVar VariationId is 12931.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC34A1	NM_003052.5	c.142_143delGCinsTT	p.Ala48Phe	missense_variant		ENST00000324417.6	NP_003043.3
SLC34A1	NM_001167579.2	c.142_143delGCinsTT	p.Ala48Phe	missense_variant			NP_001161051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC34A1	ENST00000324417.6	c.142_143delGCinsTT	p.Ala48Phe	missense_variant		1	NM_003052.5	ENSP00000321424.4
SLC34A1	ENST00000512593.5	c.142_143delGCinsTT	p.Ala48Phe	missense_variant		2		ENSP00000423022.1
SLC34A1	ENST00000504577.5	c.142_143delGCinsTT	p.Ala48Phe	missense_variant		4		ENSP00000423733.1
SLC34A1	ENST00000507685.5	n.226_227delGCinsTT		non_coding_transcript_exon_variant	Exon 3 of 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

GnomAD MNV AF: 0.00000403 AC: 1 Hom.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hypophosphatemic nephrolithiasis/osteoporosis 1 Pathogenic:1

Sep 26, 2002

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.89
Mutation Taster		=27/73	disease causing

Splicing

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

Other links and lift over

dbSNP: rs121918610; hg19: chr5-176813020;