rs111532084

Variant names:

• chr9-137232284-C-T
• rs111532084
• NM_001177316.2:c.175+123C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001177316.2(SLC34A3):​c.175+123C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0282 in 989,004 control chromosomes in the GnomAD database, including 523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (60 hom., cov: 33)
  • Exomes 𝑓: 0.029 (463 hom.)
• Consequence: SLC34A3 NM_001177316.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.38

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=-0.83).
• BP6: Variant 9-137232284-C-T is Benign according to our data. Variant chr9-137232284-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 496510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0236 (3598/152306) while in subpopulation NFE AF= 0.0368 (2501/68012). AF 95% confidence interval is 0.0356. There are 60 homozygotes in gnomad4. There are 1670 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 60 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC34A3	NM_001177316.2	c.175+123C>T		intron_variant	Intron 3 of 12	ENST00000673835.1	NP_001170787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC34A3	ENST00000673835.1	c.175+123C>T		intron_variant	Intron 3 of 12		NM_001177316.2	ENSP00000501114.1

Frequencies

GnomAD3 genomes AF: 0.0236 AC: 3596 AN: 152188 Hom.: 60 Cov.: 33

Gnomad AFR AF: 0.00613

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0196

Gnomad ASJ AF: 0.0438

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0232

Gnomad FIN AF: 0.0156

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0368

Gnomad OTH AF: 0.0282

GnomAD4 exome AF: 0.0290 AC: 24258 AN: 836698 Hom.: 463 AF XY: 0.0292 AC XY: 12656 AN XY: 433256

Gnomad4 AFR exome AF: 0.00555

Gnomad4 AMR exome AF: 0.0180

Gnomad4 ASJ exome AF: 0.0327

Gnomad4 EAS exome AF: 0.0000562

Gnomad4 SAS exome AF: 0.0221

Gnomad4 FIN exome AF: 0.0190

Gnomad4 NFE exome AF: 0.0338

Gnomad4 OTH exome AF: 0.0280

GnomAD4 genome AF: 0.0236 AC: 3598 AN: 152306 Hom.: 60 Cov.: 33 AF XY: 0.0224 AC XY: 1670 AN XY: 74476

Gnomad4 AFR AF: 0.00611

Gnomad4 AMR AF: 0.0196

Gnomad4 ASJ AF: 0.0438

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0234

Gnomad4 FIN AF: 0.0156

Gnomad4 NFE AF: 0.0368

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0297 Hom.: 10

Bravo AF: 0.0231

Asia WGS AF: 0.00693 AC: 25 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Oct 16, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: The SLC34A3 c.175+123C>T variant involves the alteration of a non-conserved intronic nucleotide with 5/5 splice prediction tools predicting no significant impact on splicing, although these predictions have yet to be functionally assessed. The variant of interest was observed in controls (from 1000 Gs) with an allele frequency of 74/5008 (1/68), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic SLC34A3 variant of 1/894 (0.001118), suggesting this variant is likely a benign polymorphism. The variant of interest was reported in one HHRH patient, but the authors considered the variant of interest a polymorphism. Additionally, one internal LCA specimen carried this variant and was homozygous for a pathogenic SLC34A3 variant, c.560+27_561-38del30. c.175+123C>T has not been reported in affected individuals or classified by other clinical labs. Therefore, taking all available lines of evidence into consideration and the high allele frequency in the general population, the variant of interest has been classified as Benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.49

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: rs111532084; hg19: chr9-140126736;