chr9-137233633-T-C

Variant names:

• chr9-137233633-T-C
• rs28407527
• NM_001177316.2:c.757T>C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001177316.2(SLC34A3):​c.757T>C​(p.Leu253Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 1,610,930 control chromosomes in the GnomAD database, including 151,484 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14178 hom., cov: 32)
  • Exomes 𝑓: 0.43 (137306 hom.)
• Consequence: SLC34A3 NM_001177316.2 splice_region, synonymous
• Scores: Splicing: ADA: 0.003826
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 1.80

Genes affected

SLC34A3 (HGNC:20305): (solute carrier family 34 member 3) This gene encodes a member of SLC34A transporter family of proteins, and is expressed primarily in the kidney. It is involved in transporting phosphate into cells via sodium cotransport in the renal brush border membrane, and contributes to the maintenance of inorganic phosphate concentration in the kidney. Mutations in this gene are associated with hereditary hypophosphatemic rickets with hypercalciuria. Alternatively spliced transcript variants varying in the 5' UTR have been found for this gene.[provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 9-137233633-T-C is Benign according to our data. Variant chr9-137233633-T-C is described in ClinVar as [Benign]. Clinvar id is 281214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137233633-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.8 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC34A3	NM_001177316.2	c.757T>C	p.Leu253Leu	splice_region_variant, synonymous_variant	Exon 8 of 13	ENST00000673835.1	NP_001170787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC34A3	ENST00000673835.1	c.757T>C	p.Leu253Leu	splice_region_variant, synonymous_variant	Exon 8 of 13		NM_001177316.2	ENSP00000501114.1
SLC34A3	ENST00000361134.2	c.757T>C	p.Leu253Leu	splice_region_variant, synonymous_variant	Exon 8 of 13	2		ENSP00000355353.2
SLC34A3	ENST00000538474.5	c.757T>C	p.Leu253Leu	splice_region_variant, synonymous_variant	Exon 8 of 13	5		ENSP00000442397.1
SLC34A3	ENST00000673865.1	c.757T>C	p.Leu253Leu	splice_region_variant, synonymous_variant	Exon 8 of 10			ENSP00000501101.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64956 AN: 151728 Hom.: 14173 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.474

GnomAD3 exomes AF: 0.451 AC: 113088 AN: 250510 Hom.: 26453 AF XY: 0.447 AC XY: 60739 AN XY: 135748

Gnomad AFR exome AF: 0.400

Gnomad AMR exome AF: 0.620

Gnomad ASJ exome AF: 0.441

Gnomad EAS exome AF: 0.487

Gnomad SAS exome AF: 0.471

Gnomad FIN exome AF: 0.361

Gnomad NFE exome AF: 0.415

Gnomad OTH exome AF: 0.441

GnomAD4 exome AF: 0.431 AC: 628292 AN: 1459084 Hom.: 137306 Cov.: 44 AF XY: 0.431 AC XY: 312768 AN XY: 725978

Gnomad4 AFR exome AF: 0.405

Gnomad4 AMR exome AF: 0.614

Gnomad4 ASJ exome AF: 0.439

Gnomad4 EAS exome AF: 0.504

Gnomad4 SAS exome AF: 0.468

Gnomad4 FIN exome AF: 0.366

Gnomad4 NFE exome AF: 0.420

Gnomad4 OTH exome AF: 0.447

GnomAD4 genome AF: 0.428 AC: 64987 AN: 151846 Hom.: 14178 Cov.: 32 AF XY: 0.433 AC XY: 32124 AN XY: 74202

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.492

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.472

Alfa AF: 0.426 Hom.: 21669

Bravo AF: 0.443

Asia WGS AF: 0.471 AC: 1642 AN: 3478

EpiCase AF: 0.429

EpiControl AF: 0.430

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:5

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 20074341) -

Jun 14, 2016

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: SLC34A3 c.757T>C (p.Leu253=) is a synonymous change that involves a non-conserved nucleotide at the Intron 7-Exon 8 boundary. One in silico tool predicts a benign outcome, and 5/5 splicing algorithms predict that this variant does not affect normal splicing, however no functional studies supporting these in silico predictions were published at the time of evaluation. This variant was found in 53912/121368 control chromosomes (12221 homozygotes) at a frequency of 0.4442028, which is approximately 251 times the estimated maximal expected allele frequency of a pathogenic SLC34A3 variant (0.0017678), suggesting this variant is likely a benign polymorphism. Additionally, the variant of interest was classified as Benign by one clinical laboratory. Taken together, the variant was classified as Benign. Taken together, the variant was classified as Benign based on the prevalence in the general population. -

not specified Benign:3

Jul 01, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Autosomal recessive hypophosphatemic bone disease Benign:1

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0038
dbscSNV1_RF	Benign	0.62
SpliceAI score (max)		0.0		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: rs28407527; hg19: chr9-140128085; COSMIC: COSV63186438; COSMIC: COSV63186438;