rs28407527

Positions:

chr9-137233633-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001177316.2(SLC34A3):c.757T>C(p.Leu253=) 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

Variant links:

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]

SLC34A3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
SLC34A3	NM_001177316.2 linkuse as main transcript	c.757T>C	p.Leu253=	splice_region_variant, synonymous_variant	8/13	ENST00000673835.1	NP_001170787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SLC34A3	ENST00000673835.1 linkuse as main transcript	c.757T>C	p.Leu253=	splice_region_variant, synonymous_variant	8/13		NM_001177316.2	ENSP00000501114	P1
SLC34A3	ENST00000361134.2 linkuse as main transcript	c.757T>C	p.Leu253=	splice_region_variant, synonymous_variant	8/13	2		ENSP00000355353	P1
SLC34A3	ENST00000538474.5 linkuse as main transcript	c.757T>C	p.Leu253=	splice_region_variant, synonymous_variant	8/13	5		ENSP00000442397	P1
SLC34A3	ENST00000673865.1 linkuse as main transcript	c.757T>C	p.Leu253=	splice_region_variant, synonymous_variant	8/10			ENSP00000501101

Frequencies

GnomAD3 genomes

AF:

0.428

AC:

64956

AN:

151728

Hom.:

14173

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.431

AC XY:

312768

AN XY:

725978

show subpopulations

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.:

AF XY:

0.433

AC XY:

32124

AN XY:

74202

show subpopulations

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

LINK: link

Submissions by phenotype

not provided

Benign:5

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jun 14, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 17, 2018	This variant is associated with the following publications: (PMID: 20074341) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 01, 2015	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Autosomal recessive hypophosphatemic bone disease

Benign:1

Benign, no assertion criteria provided

clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over