chr9-137234125-G-C

Position:

• chr9-137234125-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001177316.2(SLC34A3):​c.942G>C​(p.Ala314Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,588,666 control chromosomes in the GnomAD database, including 285 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0090 (18 hom., cov: 31)
  • Exomes 𝑓: 0.011 (267 hom.)
• Consequence: SLC34A3 NM_001177316.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.52

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=-0.83).
• BP6: Variant 9-137234125-G-C is Benign according to our data. Variant chr9-137234125-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1169030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.52 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC34A3	NM_001177316.2	c.942G>C	p.Ala314Ala	synonymous_variant	10/13	ENST00000673835.1	NP_001170787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC34A3	ENST00000673835.1	c.942G>C	p.Ala314Ala	synonymous_variant	10/13		NM_001177316.2	ENSP00000501114.1
SLC34A3	ENST00000361134.2	c.942G>C	p.Ala314Ala	synonymous_variant	10/13	2		ENSP00000355353.2
SLC34A3	ENST00000538474.5	c.942G>C	p.Ala314Ala	synonymous_variant	10/13	5		ENSP00000442397.1
SLC34A3	ENST00000673865.1	c.942G>C	p.Ala314Ala	synonymous_variant	10/10			ENSP00000501101.1

Frequencies

GnomAD3 genomes AF: 0.00902 AC: 1353 AN: 150056 Hom.: 18 Cov.: 31

Gnomad AFR AF: 0.00222

Gnomad AMI AF: 0.0198

Gnomad AMR AF: 0.00385

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.0560

Gnomad SAS AF: 0.0457

Gnomad FIN AF: 0.00594

Gnomad MID AF: 0.0160

Gnomad NFE AF: 0.00699

Gnomad OTH AF: 0.00975

GnomAD3 exomes AF: 0.0160 AC: 3500 AN: 218422 Hom.: 88 AF XY: 0.0178 AC XY: 2142 AN XY: 120194

Gnomad AFR exome AF: 0.00144

Gnomad AMR exome AF: 0.00373

Gnomad ASJ exome AF: 0.0329

Gnomad EAS exome AF: 0.0467

Gnomad SAS exome AF: 0.0470

Gnomad FIN exome AF: 0.00622

Gnomad NFE exome AF: 0.00742

Gnomad OTH exome AF: 0.0170

GnomAD4 exome AF: 0.0106 AC: 15272 AN: 1438494 Hom.: 267 Cov.: 35 AF XY: 0.0120 AC XY: 8588 AN XY: 715010

Gnomad4 AFR exome AF: 0.00195

Gnomad4 AMR exome AF: 0.00421

Gnomad4 ASJ exome AF: 0.0358

Gnomad4 EAS exome AF: 0.0450

Gnomad4 SAS exome AF: 0.0506

Gnomad4 FIN exome AF: 0.00869

Gnomad4 NFE exome AF: 0.00595

Gnomad4 OTH exome AF: 0.0155

GnomAD4 genome AF: 0.00902 AC: 1354 AN: 150172 Hom.: 18 Cov.: 31 AF XY: 0.00980 AC XY: 718 AN XY: 73242

Gnomad4 AFR AF: 0.00224

Gnomad4 AMR AF: 0.00384

Gnomad4 ASJ AF: 0.0369

Gnomad4 EAS AF: 0.0561

Gnomad4 SAS AF: 0.0458

Gnomad4 FIN AF: 0.00594

Gnomad4 NFE AF: 0.00699

Gnomad4 OTH AF: 0.00963

Alfa AF: 0.00931 Hom.: 2

Bravo AF: 0.00776

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 29, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal recessive hypophosphatemic bone disease Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jul 27, 2021	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 28, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.44

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: rs34664302; hg19: chr9-140128577;