9-137234462-C-T

Variant names:

• chr9-137234462-C-T
• rs113568956
• NM_001177316.2:c.1140C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001177316.2(SLC34A3):​c.1140C>T​(p.Leu380Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00382 in 1,599,324 control chromosomes in the GnomAD database, including 20 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. L380L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0032 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (19 hom.)
• Consequence: SLC34A3 NM_001177316.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.38
• Publications: 4 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=-0.65).
• BP6: Variant 9-137234462-C-T is Benign according to our data. Variant chr9-137234462-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 281431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.38 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00319 (486/152254) while in subpopulation NFE AF = 0.00494 (336/67998). AF 95% confidence interval is 0.00451. There are 1 homozygotes in GnomAd4. There are 233 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 19 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.1140C>T	p.Leu380Leu	synonymous	Exon 11 of 13	NP_001170787.2
	SLC34A3	NM_001177317.2		c.1140C>T	p.Leu380Leu	synonymous	Exon 11 of 13	NP_001170788.2
	SLC34A3	NM_080877.3		c.1140C>T	p.Leu380Leu	synonymous	Exon 11 of 13	NP_543153.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC34A3	ENST00000673835.1	MANE Select	c.1140C>T	p.Leu380Leu	synonymous	Exon 11 of 13	ENSP00000501114.1
	SLC34A3	ENST00000361134.2	TSL:2	c.1140C>T	p.Leu380Leu	synonymous	Exon 11 of 13	ENSP00000355353.2
	SLC34A3	ENST00000538474.5	TSL:5	c.1140C>T	p.Leu380Leu	synonymous	Exon 11 of 13	ENSP00000442397.1

Frequencies

GnomAD3 genomes AF: 0.00321 AC: 489 AN: 152136 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000773

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00496

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00377 AC: 850 AN: 225518 AF XY: 0.00391

Gnomad AFR exome AF: 0.000223

Gnomad AMR exome AF: 0.00174

Gnomad ASJ exome AF: 0.0170

Gnomad EAS exome AF: 0.0000569

Gnomad FIN exome AF: 0.00127

Gnomad NFE exome AF: 0.00535

Gnomad OTH exome AF: 0.00620

GnomAD4 exome AF: 0.00389 AC: 5626 AN: 1447070 Hom.: 19 Cov.: 35 AF XY: 0.00391 AC XY: 2818 AN XY: 720260

African (AFR) AF: 0.00108 AC: 36 AN: 33442

American (AMR) AF: 0.00184 AC: 82 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 414 AN: 26060

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39652

South Asian (SAS) AF: 0.000616 AC: 53 AN: 86104

European-Finnish (FIN) AF: 0.00162 AC: 65 AN: 40182

Middle Eastern (MID) AF: 0.0193 AC: 111 AN: 5756

European-Non Finnish (NFE) AF: 0.00411 AC: 4566 AN: 1111206

Other (OTH) AF: 0.00494 AC: 297 AN: 60100

GnomAD4 genome AF: 0.00319 AC: 486 AN: 152254 Hom.: 1 Cov.: 32 AF XY: 0.00313 AC XY: 233 AN XY: 74424

African (AFR) AF: 0.000770 AC: 32 AN: 41540

American (AMR) AF: 0.00170 AC: 26 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 58 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4832

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10620

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00494 AC: 336 AN: 67998

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00362 Hom.: 0

Bravo AF: 0.00333

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: 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

Jun 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SLC34A3: BP4, BP7

Nov 27, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 21344632)

not specified Benign:2

Jun 15, 2015

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Nov 07, 2016

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Autosomal recessive hypophosphatemic bone disease Benign:1

Mar 16, 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
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.0
DANN	Benign	0.95
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs113568956; hg19: chr9-140128914; COSMIC: COSV63187952; COSMIC: COSV63187952;