9-137234125-G-C

Variant names:

• chr9-137234125-G-C
• rs34664302
• NM_001177316.2:c.942G>C

Variant summary

Our verdict is Benign. The variant received -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 (★★). Synonymous variant affecting the same amino acid position (i.e. A314A) has been classified as Uncertain significance.

• 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
• Publications: 3 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 -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 Benign/Likely_benign. ClinVar VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC34A3	NM_001177316.2	MANE Select	c.942G>C	p.Ala314Ala	synonymous	Exon 10 of 13	NP_001170787.2
	SLC34A3	NM_001177317.2		c.942G>C	p.Ala314Ala	synonymous	Exon 10 of 13	NP_001170788.2
	SLC34A3	NM_080877.3		c.942G>C	p.Ala314Ala	synonymous	Exon 10 of 13	NP_543153.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC34A3	ENST00000673835.1	MANE Select	c.942G>C	p.Ala314Ala	synonymous	Exon 10 of 13	ENSP00000501114.1
	SLC34A3	ENST00000361134.2	TSL:2	c.942G>C	p.Ala314Ala	synonymous	Exon 10 of 13	ENSP00000355353.2
	SLC34A3	ENST00000538474.5	TSL:5	c.942G>C	p.Ala314Ala	synonymous	Exon 10 of 13	ENSP00000442397.1

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

GnomAD2 exomes AF: 0.0160 AC: 3500 AN: 218422 AF XY: 0.0178

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 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

African (AFR) AF: 0.00195 AC: 65 AN: 33312

American (AMR) AF: 0.00421 AC: 184 AN: 43746

Ashkenazi Jewish (ASJ) AF: 0.0358 AC: 928 AN: 25886

East Asian (EAS) AF: 0.0450 AC: 1763 AN: 39140

South Asian (SAS) AF: 0.0506 AC: 4280 AN: 84558

European-Finnish (FIN) AF: 0.00869 AC: 347 AN: 39918

Middle Eastern (MID) AF: 0.0384 AC: 189 AN: 4922

European-Non Finnish (NFE) AF: 0.00595 AC: 6593 AN: 1107274

Other (OTH) AF: 0.0155 AC: 923 AN: 59738

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

African (AFR) AF: 0.00224 AC: 91 AN: 40620

American (AMR) AF: 0.00384 AC: 58 AN: 15098

Ashkenazi Jewish (ASJ) AF: 0.0369 AC: 128 AN: 3470

East Asian (EAS) AF: 0.0561 AC: 283 AN: 5046

South Asian (SAS) AF: 0.0458 AC: 217 AN: 4740

European-Finnish (FIN) AF: 0.00594 AC: 61 AN: 10270

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.00699 AC: 473 AN: 67652

Other (OTH) AF: 0.00963 AC: 20 AN: 2076

Alfa AF: 0.00931 Hom.: 2

Bravo AF: 0.00776

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Autosomal recessive hypophosphatemic bone disease (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.44
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34664302; hg19: chr9-140128577;