9-137233094-G-C

Variant names:

• chr9-137233094-G-C
• rs35643193
• NM_001177316.2:c.539G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 6.69
• Publications: 7 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 288891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 SD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001177316.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC34A3	NM_001177316.2	MANE Select	c.539G>C	p.Gly180Ala	missense	Exon 6 of 13	NP_001170787.2
	SLC34A3	NM_001177317.2		c.539G>C	p.Gly180Ala	missense	Exon 6 of 13	NP_001170788.2
	SLC34A3	NM_080877.3		c.539G>C	p.Gly180Ala	missense	Exon 6 of 13	NP_543153.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC34A3	ENST00000673835.1	MANE Select	c.539G>C	p.Gly180Ala	missense	Exon 6 of 13	ENSP00000501114.1
	SLC34A3	ENST00000361134.2	TSL:2	c.539G>C	p.Gly180Ala	missense	Exon 6 of 13	ENSP00000355353.2
	SLC34A3	ENST00000538474.5	TSL:5	c.539G>C	p.Gly180Ala	missense	Exon 6 of 13	ENSP00000442397.1

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1797 AN: 152108 Hom.: 16 Cov.: 33

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

GnomAD2 exomes AF: 0.0129 AC: 3221 AN: 248880 AF XY: 0.0139

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 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.: 44 AF XY: 0.0161 AC XY: 11712 AN XY: 725640

African (AFR) AF: 0.00254 AC: 85 AN: 33422

American (AMR) AF: 0.00982 AC: 439 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00486 AC: 127 AN: 26122

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.0127 AC: 1097 AN: 86138

European-Finnish (FIN) AF: 0.00985 AC: 514 AN: 52158

Middle Eastern (MID) AF: 0.0214 AC: 96 AN: 4488

European-Non Finnish (NFE) AF: 0.0181 AC: 20133 AN: 1111778

Other (OTH) AF: 0.0134 AC: 804 AN: 60220

GnomAD4 genome AF: 0.0118 AC: 1796 AN: 152226 Hom.: 16 Cov.: 33 AF XY: 0.0118 AC XY: 881 AN XY: 74450

African (AFR) AF: 0.00339 AC: 141 AN: 41560

American (AMR) AF: 0.0106 AC: 162 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00605 AC: 21 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.0118 AC: 57 AN: 4826

European-Finnish (FIN) AF: 0.0107 AC: 113 AN: 10610

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0182 AC: 1240 AN: 67978

Other (OTH) AF: 0.0161 AC: 34 AN: 2110

Alfa AF: 0.0163 Hom.: 9

Bravo AF: 0.0115

TwinsUK AF: 0.0175 AC: 65

ALSPAC AF: 0.0218 AC: 84

ESP6500AA AF: 0.00341 AC: 15

ESP6500EA AF: 0.0186 AC: 160

ExAC AF: 0.0136 AC: 1647

Asia WGS AF: 0.00520 AC: 18 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

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jun 17, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

Jul 07, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Autosomal recessive hypophosphatemic bone disease Benign:1

Nov 28, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.74	D
Eigen	Benign	-0.022
Eigen_PC	Benign	0.057
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.0092	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		6.7
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.073
Sift	Benign	0.065	T
Sift4G	Benign	0.12	T
Polyphen		0.15	B
Vest4		0.25
MPC		0.048
ClinPred		0.060	T
GERP RS		3.6
Varity_R		0.30
gMVP		0.50
Mutation Taster		=45/55	disease causing

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

Other links and lift over

dbSNP: rs35643193; hg19: chr9-140127546; COSMIC: COSV63187801; COSMIC: COSV63187801;