rs28591989

Positions:

• chr9-137236430-A-C
• chr9-137236430-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001177316.2(SLC34A3):​c.*14A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,534,196 control chromosomes in the GnomAD database, including 129,849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12188 hom., cov: 33)
  • Exomes 𝑓: 0.41 (117661 hom.)
• Consequence: SLC34A3 NM_001177316.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -4.56

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 9-137236430-A-C is Benign according to our data. Variant chr9-137236430-A-C is described in ClinVar as [Benign]. Clinvar id is 194276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137236430-A-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC34A3	NM_001177316.2	c.*14A>C		3_prime_UTR_variant	13/13	ENST00000673835.1	NP_001170787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC34A3	ENST00000673835.1	c.*14A>C		3_prime_UTR_variant	13/13		NM_001177316.2	ENSP00000501114	P1
SLC34A3	ENST00000361134.2	c.*14A>C		3_prime_UTR_variant	13/13	2		ENSP00000355353	P1
SLC34A3	ENST00000538474.5	c.*14A>C		3_prime_UTR_variant	13/13	5		ENSP00000442397	P1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60144 AN: 151946 Hom.: 12178 Cov.: 33

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.386

GnomAD3 exomes AF: 0.380 AC: 54111 AN: 142348 Hom.: 10770 AF XY: 0.377 AC XY: 28701 AN XY: 76218

Gnomad AFR exome AF: 0.407

Gnomad AMR exome AF: 0.410

Gnomad ASJ exome AF: 0.428

Gnomad EAS exome AF: 0.146

Gnomad SAS exome AF: 0.356

Gnomad FIN exome AF: 0.287

Gnomad NFE exome AF: 0.421

Gnomad OTH exome AF: 0.386

GnomAD4 exome AF: 0.409 AC: 565204 AN: 1382132 Hom.: 117661 Cov.: 35 AF XY: 0.408 AC XY: 278301 AN XY: 682268

Gnomad4 AFR exome AF: 0.421

Gnomad4 AMR exome AF: 0.402

Gnomad4 ASJ exome AF: 0.427

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.355

Gnomad4 FIN exome AF: 0.294

Gnomad4 NFE exome AF: 0.426

Gnomad4 OTH exome AF: 0.390

GnomAD4 genome AF: 0.396 AC: 60176 AN: 152064 Hom.: 12188 Cov.: 33 AF XY: 0.386 AC XY: 28722 AN XY: 74360

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.382

Alfa AF: 0.319 Hom.: 1290

Bravo AF: 0.405

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 09, 2014	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jun 14, 2016	Variant summary: The SLC34A3 c.*14A>C variant is located in the 3' UTR at a non-conserved nucleotide. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 7130/17986 (1/2, 1453 homozygotes), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic SLC34A3 variant of 1/894. A reputable clinical laboratory cites the variant as benign. Therefore, taking all available lines of evidence into consideration, the variant of interest is classifed as Benign. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.22
DANN	Benign	0.50

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

Other links and lift over

dbSNP: rs28591989; hg19: chr9-140130882; COSMIC: COSV61163671; COSMIC: COSV61163671;