9-137236154-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001177316.2(SLC34A3):c.1538A>T(p.Glu513Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 1,609,720 control chromosomes in the GnomAD database, including 593,168 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E513Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.89 ( 60559 hom., cov: 34)

Exomes 𝑓: 0.85 ( 532609 hom. )

Consequence

SLC34A3
NM_001177316.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0850

Publications

27 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.457051E-7).

BP6

Variant 9-137236154-A-T is Benign according to our data. Variant chr9-137236154-A-T is described in ClinVar as Benign. ClinVar VariationId is 194277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC34A3	NM_001177316.2 link	c.1538A>T	p.Glu513Val	missense_variant	Exon 13 of 13	ENST00000673835.1	NP_001170787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SLC34A3	ENST00000673835.1 link	c.1538A>T	p.Glu513Val	missense_variant	Exon 13 of 13		NM_001177316.2	ENSP00000501114.1
SLC34A3	ENST00000361134.2 link	c.1538A>T	p.Glu513Val	missense_variant	Exon 13 of 13	2		ENSP00000355353.2
SLC34A3	ENST00000538474.5 link	c.1538A>T	p.Glu513Val	missense_variant	Exon 13 of 13	5		ENSP00000442397.1

Frequencies

GnomAD3 genomes

AF:

0.889

AC:

135208

AN:

152136

Hom.:

60498

Cov.:

show subpopulations

Gnomad AFR

AF:

0.971

Gnomad AMI

AF:

0.842

Gnomad AMR

AF:

0.932

Gnomad ASJ

AF:

0.908

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.936

Gnomad FIN

AF:

0.733

Gnomad MID

AF:

0.940

Gnomad NFE

AF:

0.840

Gnomad OTH

AF:

0.910

GnomAD2 exomes

AF:

0.882

AC:

211353

AN:

239692

AF XY:

0.880

show subpopulations

Gnomad AFR exome

AF:

0.975

Gnomad AMR exome

AF:

0.944

Gnomad ASJ exome

AF:

0.903

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.740

Gnomad NFE exome

AF:

0.837

Gnomad OTH exome

AF:

0.876

GnomAD4 exome

AF:

0.853

AC:

1243773

AN:

1457466

Hom.:

532609

Cov.:

AF XY:

0.855

AC XY:

620212

AN XY:

725086

show subpopulations

African (AFR)

AF:

0.978

AC:

32709

AN:

33452

American (AMR)

AF:

0.944

AC:

42110

AN:

44628

Ashkenazi Jewish (ASJ)

AF:

0.900

AC:

23457

AN:

26068

East Asian (EAS)

AF:

1.00

AC:

39665

AN:

39676

South Asian (SAS)

AF:

0.936

AC:

80664

AN:

86168

European-Finnish (FIN)

AF:

0.747

AC:

37497

AN:

50204

Middle Eastern (MID)

AF:

0.932

AC:

5373

AN:

5762

European-Non Finnish (NFE)

AF:

0.836

AC:

929444

AN:

1111240

Other (OTH)

AF:

0.877

AC:

52854

AN:

60268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

11902

23804

35707

47609

59511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21126

42252

63378

84504

105630

<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:

0.889

AC:

135328

AN:

152254

Hom.:

60559

Cov.:

AF XY:

0.887

AC XY:

65997

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.971

AC:

40357

AN:

41572

American (AMR)

AF:

0.932

AC:

14266

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.908

AC:

3154

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5177

AN:

5184

South Asian (SAS)

AF:

0.937

AC:

4521

AN:

4826

European-Finnish (FIN)

AF:

0.733

AC:

7760

AN:

10590

Middle Eastern (MID)

AF:

0.942

AC:

277

AN:

294

European-Non Finnish (NFE)

AF:

0.840

AC:

57120

AN:

67986

Other (OTH)

AF:

0.911

AC:

1928

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

768

1535

2303

3070

3838

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

900

1800

2700

3600

4500

<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:

0.860

Hom.:

18210

Bravo

AF:

0.908

TwinsUK

AF:

0.830

AC:

3079

ALSPAC

AF:

0.833

AC:

3212

ESP6500AA

AF:

0.969

AC:

4118

ESP6500EA

AF:

0.845

AC:

7043

ExAC

AF:

0.877

AC:

104330

Asia WGS

AF:

0.970

AC:

3375

AN:

3478

EpiCase

AF:

0.854

EpiControl

AF:

0.849

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Nov 03, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Mar 21, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Glu513Val in exon 13 of SLC34A3: This variant is not expected to have clinical significance because it has been identified in 99.94% (8411/8416) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitu te.org; dbSNP rs28542318).

not provided

Benign:2

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

Autosomal recessive hypophosphatemic bone disease

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.2

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.30

T;.

MetaRNN

Benign

8.5e-7

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-3.3

N;N

PhyloP100

0.085

PrimateAI

Uncertain

0.56

PROVEAN

Benign

3.8

N;N

REVEL

Benign

0.097

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Vest4

0.071

ClinPred

0.0016

GERP RS

4.2

Varity_R

0.060

gMVP

0.45

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

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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