9-137234192-G-A

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.1009G>A(p.Gly337Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,605,816 control chromosomes in the GnomAD database, including 416 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 (★★). Synonymous variant affecting the same amino acid position (i.e. G337G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.012 ( 33 hom., cov: 31)

Exomes 𝑓: 0.012 ( 383 hom. )

Consequence

SLC34A3
NM_001177316.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.13

Publications

14 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=0.0019162893).

BP6

Variant 9-137234192-G-A is Benign according to our data. Variant chr9-137234192-G-A is described in ClinVar as Benign. ClinVar VariationId is 193754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC34A3	NM_001177316.2 link	c.1009G>A	p.Gly337Ser	missense_variant	Exon 10 of 13	ENST00000673835.1	NP_001170787.2	Q8N130

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC34A3	ENST00000673835.1 link	c.1009G>A	p.Gly337Ser	missense_variant	Exon 10 of 13		NM_001177316.2	ENSP00000501114.1	Q8N130
SLC34A3	ENST00000361134.2 link	c.1009G>A	p.Gly337Ser	missense_variant	Exon 10 of 13	2		ENSP00000355353.2	Q8N130
SLC34A3	ENST00000538474.5 link	c.1009G>A	p.Gly337Ser	missense_variant	Exon 10 of 13	5		ENSP00000442397.1	Q8N130
SLC34A3	ENST00000673865.1 link	c.1009G>A	p.Gly337Ser	missense_variant	Exon 10 of 10			ENSP00000501101.1	A0A669KB63

Frequencies

GnomAD3 genomes

AF:

0.0119

AC:

1816

AN:

151998

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00756

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.00589

Gnomad ASJ

AF:

0.0377

Gnomad EAS

AF:

0.0816

Gnomad SAS

AF:

0.0559

Gnomad FIN

AF:

0.00574

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00711

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.0205

AC:

4819

AN:

235040

AF XY:

0.0221

show subpopulations

Gnomad AFR exome

AF:

0.00901

Gnomad AMR exome

AF:

0.00467

Gnomad ASJ exome

AF:

0.0336

Gnomad EAS exome

AF:

0.0777

Gnomad FIN exome

AF:

0.00702

Gnomad NFE exome

AF:

0.00868

Gnomad OTH exome

AF:

0.0203

GnomAD4 exome

AF:

0.0123

AC:

17894

AN:

1453700

Hom.:

383

Cov.:

AF XY:

0.0138

AC XY:

9975

AN XY:

722838

show subpopulations

African (AFR)

AF:

0.00838

AC:

280

AN:

33414

American (AMR)

AF:

0.00495

AC:

219

AN:

44204

Ashkenazi Jewish (ASJ)

AF:

0.0363

AC:

944

AN:

25980

East Asian (EAS)

AF:

0.0693

AC:

2735

AN:

39444

South Asian (SAS)

AF:

0.0593

AC:

5055

AN:

85288

European-Finnish (FIN)

AF:

0.00851

AC:

421

AN:

49500

Middle Eastern (MID)

AF:

0.0395

AC:

227

AN:

5748

European-Non Finnish (NFE)

AF:

0.00620

AC:

6877

AN:

1109998

Other (OTH)

AF:

0.0189

AC:

1136

AN:

60124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

1159

2317

3476

4634

5793

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

326

652

978

1304

1630

<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:

0.0120

AC:

1820

AN:

152116

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

975

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.00761

AC:

316

AN:

41500

American (AMR)

AF:

0.00589

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0377

AC:

131

AN:

3472

East Asian (EAS)

AF:

0.0820

AC:

423

AN:

5160

South Asian (SAS)

AF:

0.0560

AC:

269

AN:

4806

European-Finnish (FIN)

AF:

0.00574

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00711

AC:

483

AN:

67950

Other (OTH)

AF:

0.0114

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

177

265

354

442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.0114

Hom.:

Bravo

AF:

0.0111

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.00798

AC:

ESP6500EA

AF:

0.00698

AC:

ExAC

AF:

0.0204

AC:

2452

Asia WGS

AF:

0.0660

AC:

229

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Apr 27, 2015

Eurofins Ntd Llc (ga)

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

0.067

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.20

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.74

T;.

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.24

N;N

PhyloP100

-2.1

PrimateAI

Benign

0.48

PROVEAN

Benign

1.8

N;N

REVEL

Benign

0.029

Sift

Benign

0.74

T;T

Sift4G

Benign

0.87

T;T

Polyphen

0.0050

B;B

Vest4

0.031

MPC

0.040

ClinPred

0.0019

GERP RS

-7.2

Varity_R

0.038

gMVP

0.53

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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