rs35699762

Positions:

chr9-137234192-G-A

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 -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 id is 193754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137234192-G-A is described in Lovd as [Likely_benign].

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/exons	MANE	Protein	UniProt
SLC34A3	NM_001177316.2 linkuse as main transcript	c.1009G>A	p.Gly337Ser	missense_variant	10/13	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.1009G>A	p.Gly337Ser	missense_variant	10/13		NM_001177316.2	ENSP00000501114	P1
SLC34A3	ENST00000361134.2 linkuse as main transcript	c.1009G>A	p.Gly337Ser	missense_variant	10/13	2		ENSP00000355353	P1
SLC34A3	ENST00000538474.5 linkuse as main transcript	c.1009G>A	p.Gly337Ser	missense_variant	10/13	5		ENSP00000442397	P1
SLC34A3	ENST00000673865.1 linkuse as main transcript	c.1009G>A	p.Gly337Ser	missense_variant	10/10			ENSP00000501101

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

GnomAD3 exomes

AF:

0.0205

AC:

4819

AN:

235040

Hom.:

135

AF XY:

0.0221

AC XY:

2829

AN XY:

128042

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 SAS exome

AF:

0.0569

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

Gnomad4 AFR exome

AF:

0.00838

Gnomad4 AMR exome

AF:

0.00495

Gnomad4 ASJ exome

AF:

0.0363

Gnomad4 EAS exome

AF:

0.0693

Gnomad4 SAS exome

AF:

0.0593

Gnomad4 FIN exome

AF:

0.00851

Gnomad4 NFE exome

AF:

0.00620

Gnomad4 OTH exome

AF:

0.0189

GnomAD4 genome

AF:

0.0120

AC:

1820

AN:

152116

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

975

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00761

Gnomad4 AMR

AF:

0.00589

Gnomad4 ASJ

AF:

0.0377

Gnomad4 EAS

AF:

0.0820

Gnomad4 SAS

AF:

0.0560

Gnomad4 FIN

AF:

0.00574

Gnomad4 NFE

AF:

0.00711

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.0115

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Apr 27, 2015

- -

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

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

MutationTaster

Benign

1.0

N;N

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

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

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