rs1554095568

chr5-177388370-C-T

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_003052.5(SLC34A1):c.934C>T(p.Gln312Ter) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC34A1 NM_003052.5 stop_gained, splice_region
• Scores: Splicing: ADA: 0.005653
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 0.841

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 Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 5-177388370-C-T is Pathogenic according to our data. Variant chr5-177388370-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 433538.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC34A1	NM_003052.5	c.934C>T	p.Gln312Ter	stop_gained, splice_region_variant	8/13	ENST00000324417.6
SLC34A1	NM_001167579.2	c.934C>T	p.Gln312Ter	stop_gained, splice_region_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC34A1	ENST00000324417.6	c.934C>T	p.Gln312Ter	stop_gained, splice_region_variant	8/13	1	NM_003052.5	P1
SLC34A1	ENST00000512593.5	c.934C>T	p.Gln312Ter	stop_gained, splice_region_variant	8/9	2
SLC34A1	ENST00000507685.5	n.1225C>T		splice_region_variant, non_coding_transcript_exon_variant	6/10	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hypophosphatemic nephrolithiasis/osteoporosis 1 Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Shenzhen Institute of Pediatrics, Shenzhen Children's Hospital

Aug 11, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.28
Cadd	Pathogenic	35
Dann	Benign	0.90
Eigen	Benign	0.11
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.50	N
MutationTaster	Benign	1.0	A;D
Vest4		0.41
GERP RS		1.4

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0057
dbscSNV1_RF	Benign	0.24
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1554095568; hg19: chr5-176815371;