9-137233633-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Publications

18 publications found

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 Gene-Disease associations (from GenCC):

hereditary hypophosphatemic rickets with hypercalciuria
Inheritance: SD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

SLC34A3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 281214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 link	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
SLC34A3	ENST00000673835.1 link	c.757T>C	p.Leu253Leu	splice_region_variant, synonymous_variant	Exon 8 of 13		NM_001177316.2	ENSP00000501114.1
SLC34A3	ENST00000361134.2 link	c.757T>C	p.Leu253Leu	splice_region_variant, synonymous_variant	Exon 8 of 13	2		ENSP00000355353.2
SLC34A3	ENST00000538474.5 link	c.757T>C	p.Leu253Leu	splice_region_variant, synonymous_variant	Exon 8 of 13	5		ENSP00000442397.1
SLC34A3	ENST00000673865.1 link	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.:

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

GnomAD2 exomes

AF:

0.451

AC:

113088

AN:

250510

AF XY:

0.447

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 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

African (AFR)

AF:

0.405

AC:

13556

AN:

33446

American (AMR)

AF:

0.614

AC:

27431

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.439

AC:

11471

AN:

26124

East Asian (EAS)

AF:

0.504

AC:

19997

AN:

39688

South Asian (SAS)

AF:

0.468

AC:

40367

AN:

86234

European-Finnish (FIN)

AF:

0.366

AC:

19109

AN:

52228

Middle Eastern (MID)

AF:

0.468

AC:

2685

AN:

5742

European-Non Finnish (NFE)

AF:

0.420

AC:

466718

AN:

1110574

Other (OTH)

AF:

0.447

AC:

26958

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

22090

44179

66269

88358

110448

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14500

29000

43500

58000

72500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.428

AC:

64987

AN:

151846

Hom.:

14178

Cov.:

AF XY:

0.433

AC XY:

32124

AN XY:

74202

show subpopulations

African (AFR)

AF:

0.402

AC:

16655

AN:

41404

American (AMR)

AF:

0.559

AC:

8532

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.439

AC:

1520

AN:

3466

East Asian (EAS)

AF:

0.492

AC:

2523

AN:

5124

South Asian (SAS)

AF:

0.486

AC:

2344

AN:

4826

European-Finnish (FIN)

AF:

0.362

AC:

3820

AN:

10564

Middle Eastern (MID)

AF:

0.500

AC:

146

AN:

292

European-Non Finnish (NFE)

AF:

0.414

AC:

28128

AN:

67890

Other (OTH)

AF:

0.472

AC:

995

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1967

3933

5900

7866

9833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

616

1232

1848

2464

3080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.426

Hom.:

48285

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

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

- -

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. -

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) -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:3

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

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

- -

Jul 01, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

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

(source)

DANN

Benign

0.65

PhyloP100

1.8

Mutation Taster

=52/48

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over