rs34372115

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.200G>A(p.Arg67His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.089 in 1,609,484 control chromosomes in the GnomAD database, including 7,480 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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. R67C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.073 ( 587 hom., cov: 33)

Exomes 𝑓: 0.091 ( 6893 hom. )

Consequence

SLC34A3
NM_001177316.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0290

Publications

19 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=0.002386719).

BP6

Variant 9-137232599-G-A is Benign according to our data. Variant chr9-137232599-G-A is described in ClinVar as Benign. ClinVar VariationId is 504911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC34A3	NM_001177316.2 link	c.200G>A	p.Arg67His	missense_variant	Exon 4 of 13	ENST00000673835.1	NP_001170787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC34A3	ENST00000673835.1 link	c.200G>A	p.Arg67His	missense_variant	Exon 4 of 13		NM_001177316.2	ENSP00000501114.1

Frequencies

GnomAD3 genomes

AF:

0.0732

AC:

11091

AN:

151592

Hom.:

589

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0151

Gnomad AMI

AF:

0.0602

Gnomad AMR

AF:

0.0548

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.198

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.0733

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.0944

Gnomad OTH

AF:

0.0963

GnomAD2 exomes

AF:

0.0987

AC:

24067

AN:

243734

AF XY:

0.105

show subpopulations

Gnomad AFR exome

AF:

0.0138

Gnomad AMR exome

AF:

0.0478

Gnomad ASJ exome

AF:

0.126

Gnomad EAS exome

AF:

0.209

Gnomad FIN exome

AF:

0.0775

Gnomad NFE exome

AF:

0.0957

Gnomad OTH exome

AF:

0.108

GnomAD4 exome

AF:

0.0907

AC:

132217

AN:

1457780

Hom.:

6893

Cov.:

AF XY:

0.0937

AC XY:

67932

AN XY:

725198

show subpopulations

African (AFR)

AF:

0.0137

AC:

454

AN:

33162

American (AMR)

AF:

0.0512

AC:

2283

AN:

44600

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

3247

AN:

26082

East Asian (EAS)

AF:

0.183

AC:

7215

AN:

39468

South Asian (SAS)

AF:

0.145

AC:

12473

AN:

86028

European-Finnish (FIN)

AF:

0.0792

AC:

4116

AN:

51952

Middle Eastern (MID)

AF:

0.178

AC:

1023

AN:

5758

European-Non Finnish (NFE)

AF:

0.0862

AC:

95673

AN:

1110526

Other (OTH)

AF:

0.0952

AC:

5733

AN:

60204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

8040

16079

24119

32158

40198

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3478

6956

10434

13912

17390

<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:

0.0730

AC:

11076

AN:

151704

Hom.:

587

Cov.:

AF XY:

0.0735

AC XY:

5456

AN XY:

74194

show subpopulations

African (AFR)

AF:

0.0150

AC:

619

AN:

41176

American (AMR)

AF:

0.0547

AC:

835

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.130

AC:

450

AN:

3472

East Asian (EAS)

AF:

0.197

AC:

1020

AN:

5166

South Asian (SAS)

AF:

0.137

AC:

661

AN:

4820

European-Finnish (FIN)

AF:

0.0733

AC:

779

AN:

10622

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0944

AC:

6409

AN:

67926

Other (OTH)

AF:

0.0963

AC:

202

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

522

1044

1565

2087

2609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.0755

Hom.:

142

Bravo

AF:

0.0688

TwinsUK

AF:

0.0763

AC:

283

ALSPAC

AF:

0.0913

AC:

352

ESP6500AA

AF:

0.0164

AC:

ESP6500EA

AF:

0.0895

AC:

766

ExAC

AF:

0.0989

AC:

11924

EpiCase

AF:

0.103

EpiControl

AF:

0.105

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Nov 07, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 22387237, 18480181, 21344632, 16358215, 27939817, 28095294)

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:1

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.Arg67His in exon 4 of SLC34A3: This variant is not expected to have clinical s ignificance because it has been identified in 21.63% (1799/8318) of East Asian c hromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute .org; dbSNP rs34372115).

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.4

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.19

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.47

T;.

MetaRNN

Benign

0.0024

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;L

PhyloP100

0.029

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.018

Sift

Benign

0.58

T;T

Sift4G

Benign

0.45

T;T

Vest4

0.060

ClinPred

0.015

GERP RS

-7.5

Varity_R

0.029

gMVP

0.51

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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