rs34372115

Positions:

Variant summary

Our verdict is Benign. Variant got -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. 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 0.073 ( 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

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=0.002386719).

BP6

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

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/exons	MANE	Protein	UniProt
SLC34A3	NM_001177316.2 linkuse as main transcript	c.200G>A	p.Arg67His	missense_variant	4/13	ENST00000673835.1	NP_001170787.2	Q8N130

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC34A3	ENST00000673835.1 linkuse as main transcript	c.200G>A	p.Arg67His	missense_variant	4/13		NM_001177316.2	ENSP00000501114.1		Q8N130

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

GnomAD3 exomes

AF:

0.0987

AC:

24067

AN:

243734

Hom.:

1544

AF XY:

0.105

AC XY:

13988

AN XY:

133104

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 SAS exome

AF:

0.149

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

Gnomad4 AFR exome

AF:

0.0137

Gnomad4 AMR exome

AF:

0.0512

Gnomad4 ASJ exome

AF:

0.124

Gnomad4 EAS exome

AF:

0.183

Gnomad4 SAS exome

AF:

0.145

Gnomad4 FIN exome

AF:

0.0792

Gnomad4 NFE exome

AF:

0.0862

Gnomad4 OTH exome

AF:

0.0952

GnomAD4 genome

AF:

0.0730

AC:

11076

AN:

151704

Hom.:

587

Cov.:

AF XY:

0.0735

AC XY:

5456

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.0150

Gnomad4 AMR

AF:

0.0547

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.197

Gnomad4 SAS

AF:

0.137

Gnomad4 FIN

AF:

0.0733

Gnomad4 NFE

AF:

0.0944

Gnomad4 OTH

AF:

0.0963

Alfa

AF:

0.0761

Hom.:

141

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

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	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 07, 2018	This variant is associated with the following publications: (PMID: 22387237, 18480181, 21344632, 16358215, 27939817, 28095294) -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 21, 2016

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

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

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

Polyphen

0.0070

B;B

Vest4

0.060

MPC

0.046

ClinPred

0.015

GERP RS

-7.5

Varity_R

0.029

gMVP

0.51

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

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