rs35643193

Positions:

chr9-137233094-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001177316.2(SLC34A3):c.539G>C(p.Gly180Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0156 in 1,610,926 control chromosomes in the GnomAD database, including 242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 16 hom., cov: 33)

Exomes 𝑓: 0.016 ( 226 hom. )

Consequence

SLC34A3
NM_001177316.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 6.69

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=0.009243995).

BP6

Variant 9-137233094-G-C is Benign according to our data. Variant chr9-137233094-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 288891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137233094-G-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0118 (1796/152226) while in subpopulation NFE AF= 0.0182 (1240/67978). AF 95% confidence interval is 0.0174. There are 16 homozygotes in gnomad4. There are 881 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC34A3	NM_001177316.2 linkuse as main transcript	c.539G>C	p.Gly180Ala	missense_variant	6/13	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.539G>C	p.Gly180Ala	missense_variant	6/13		NM_001177316.2	ENSP00000501114.1	Q8N130
SLC34A3	ENST00000361134.2 linkuse as main transcript	c.539G>C	p.Gly180Ala	missense_variant	6/13	2		ENSP00000355353.2	Q8N130
SLC34A3	ENST00000538474.5 linkuse as main transcript	c.539G>C	p.Gly180Ala	missense_variant	6/13	5		ENSP00000442397.1	Q8N130
SLC34A3	ENST00000673865.1 linkuse as main transcript	c.539G>C	p.Gly180Ala	missense_variant	6/10			ENSP00000501101.1	A0A669KB63

Frequencies

GnomAD3 genomes

AF:

0.0118

AC:

1797

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00340

Gnomad AMI

AF:

0.0242

Gnomad AMR

AF:

0.0106

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.0107

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0182

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.0129

AC:

3221

AN:

248880

Hom.:

AF XY:

0.0139

AC XY:

1885

AN XY:

135268

show subpopulations

Gnomad AFR exome

AF:

0.00250

Gnomad AMR exome

AF:

0.00949

Gnomad ASJ exome

AF:

0.00481

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0136

Gnomad FIN exome

AF:

0.00926

Gnomad NFE exome

AF:

0.0187

Gnomad OTH exome

AF:

0.0153

GnomAD4 exome

AF:

0.0160

AC:

23296

AN:

1458700

Hom.:

226

Cov.:

AF XY:

0.0161

AC XY:

11712

AN XY:

725640

show subpopulations

Gnomad4 AFR exome

AF:

0.00254

Gnomad4 AMR exome

AF:

0.00982

Gnomad4 ASJ exome

AF:

0.00486

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0127

Gnomad4 FIN exome

AF:

0.00985

Gnomad4 NFE exome

AF:

0.0181

Gnomad4 OTH exome

AF:

0.0134

GnomAD4 genome

AF:

0.0118

AC:

1796

AN:

152226

Hom.:

Cov.:

AF XY:

0.0118

AC XY:

881

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00339

Gnomad4 AMR

AF:

0.0106

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0118

Gnomad4 FIN

AF:

0.0107

Gnomad4 NFE

AF:

0.0182

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0163

Hom.:

Bravo

AF:

0.0115

TwinsUK

AF:

0.0175

AC:

ALSPAC

AF:

0.0218

AC:

ESP6500AA

AF:

0.00341

AC:

ESP6500EA

AF:

0.0186

AC:

160

ExAC

AF:

0.0136

AC:

1647

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.0190

EpiControl

AF:

0.0201

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 17, 2020	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jul 07, 2016

- -

Autosomal recessive hypophosphatemic bone disease

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 28, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.74

D;D

Eigen

Benign

-0.022

Eigen_PC

Benign

0.057

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.91

D;.

MetaRNN

Benign

0.0092

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-4.2

D;D

REVEL

Benign

0.073

Sift

Benign

0.065

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.15

B;B

Vest4

0.25

MPC

0.048

ClinPred

0.060

GERP RS

3.6

Varity_R

0.30

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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