9-137236154-A-T

Position:

chr9-137236154-A-T

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

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=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 id is 194277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137236154-A-T is described in Lovd as [Benign]. Variant chr9-137236154-A-T is described in Lovd as [Likely_benign].

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/exons	MANE	Protein	UniProt
SLC34A3	NM_001177316.2 linkuse as main transcript	c.1538A>T	p.Glu513Val	missense_variant	13/13	ENST00000673835.1	NP_001170787.2	Q8N130

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC34A3	ENST00000673835.1 linkuse as main transcript	c.1538A>T	p.Glu513Val	missense_variant	13/13		NM_001177316.2	ENSP00000501114.1	Q8N130
SLC34A3	ENST00000361134.2 linkuse as main transcript	c.1538A>T	p.Glu513Val	missense_variant	13/13	2		ENSP00000355353.2	Q8N130
SLC34A3	ENST00000538474.5 linkuse as main transcript	c.1538A>T	p.Glu513Val	missense_variant	13/13	5		ENSP00000442397.1	Q8N130

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

GnomAD3 exomes

AF:

0.882

AC:

211353

AN:

239692

Hom.:

93815

AF XY:

0.880

AC XY:

115667

AN XY:

131382

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 SAS exome

AF:

0.938

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

Gnomad4 AFR exome

AF:

0.978

Gnomad4 AMR exome

AF:

0.944

Gnomad4 ASJ exome

AF:

0.900

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.936

Gnomad4 FIN exome

AF:

0.747

Gnomad4 NFE exome

AF:

0.836

Gnomad4 OTH exome

AF:

0.877

GnomAD4 genome

AF:

0.889

AC:

135328

AN:

152254

Hom.:

60559

Cov.:

AF XY:

0.887

AC XY:

65997

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.971

Gnomad4 AMR

AF:

0.932

Gnomad4 ASJ

AF:

0.908

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.937

Gnomad4 FIN

AF:

0.733

Gnomad4 NFE

AF:

0.840

Gnomad4 OTH

AF:

0.911

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

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 03, 2014	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 21, 2016	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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Autosomal recessive hypophosphatemic bone disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

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

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

MutationTaster

Benign

1.0

P;P

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

Polyphen

0.0

B;B

Vest4

0.071

MPC

0.044

ClinPred

0.0016

GERP RS

4.2

Varity_R

0.060

gMVP

0.45

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

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