9-137233273-C-T

Position:

• chr9-137233273-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001177316.2(SLC34A3):​c.625C>T​(p.Leu209Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00609 in 1,584,374 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0041 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0063 (37 hom.)
• Consequence: SLC34A3 NM_001177316.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.214

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 9-137233273-C-T is Benign according to our data. Variant chr9-137233273-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 504908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137233273-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.214 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00413 (628/152242) while in subpopulation NFE AF= 0.00776 (528/68002). AF 95% confidence interval is 0.00722. There are 1 homozygotes in gnomad4. There are 276 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC34A3	NM_001177316.2	c.625C>T	p.Leu209Leu	synonymous_variant	7/13	ENST00000673835.1	NP_001170787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC34A3	ENST00000673835.1	c.625C>T	p.Leu209Leu	synonymous_variant	7/13		NM_001177316.2	ENSP00000501114.1
SLC34A3	ENST00000361134.2	c.625C>T	p.Leu209Leu	synonymous_variant	7/13	2		ENSP00000355353.2
SLC34A3	ENST00000538474.5	c.625C>T	p.Leu209Leu	synonymous_variant	7/13	5		ENSP00000442397.1
SLC34A3	ENST00000673865.1	c.625C>T	p.Leu209Leu	synonymous_variant	7/10			ENSP00000501101.1

Frequencies

GnomAD3 genomes AF: 0.00413 AC: 628 AN: 152124 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00776

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00365 AC: 724 AN: 198322 Hom.: 2 AF XY: 0.00371 AC XY: 401 AN XY: 108018

Gnomad AFR exome AF: 0.000784

Gnomad AMR exome AF: 0.000732

Gnomad ASJ exome AF: 0.000331

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000190

Gnomad FIN exome AF: 0.000635

Gnomad NFE exome AF: 0.00775

Gnomad OTH exome AF: 0.00448

GnomAD4 exome AF: 0.00630 AC: 9019 AN: 1432132 Hom.: 37 Cov.: 36 AF XY: 0.00592 AC XY: 4203 AN XY: 710152

Gnomad4 AFR exome AF: 0.00143

Gnomad4 AMR exome AF: 0.000827

Gnomad4 ASJ exome AF: 0.000391

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000133

Gnomad4 FIN exome AF: 0.00147

Gnomad4 NFE exome AF: 0.00784

Gnomad4 OTH exome AF: 0.00406

GnomAD4 genome AF: 0.00413 AC: 628 AN: 152242 Hom.: 1 Cov.: 32 AF XY: 0.00371 AC XY: 276 AN XY: 74438

Gnomad4 AFR AF: 0.00142

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00776

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00612 Hom.: 1

Bravo AF: 0.00408

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2023	SLC34A3: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 27, 2021	This variant is associated with the following publications: (PMID: 16358215) -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 21, 2016

p.Leu209Leu in exon 7 of SLC34A3: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 1.62% (257/15850) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org; dbSNP rs34796681). -

Autosomal recessive hypophosphatemic bone disease Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Oct 16, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.3
DANN	Benign	0.95

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: rs34796681; hg19: chr9-140127725;