9-137231952-C-T

Position:

• chr9-137231952-C-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.86-120C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,169,576 control chromosomes in the GnomAD database, including 141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (10 hom., cov: 33)
  • Exomes 𝑓: 0.014 (131 hom.)
• Consequence: SLC34A3 NM_001177316.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.19

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=-0.9).
• BP6: Variant 9-137231952-C-T is Benign according to our data. Variant chr9-137231952-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1213253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137231952-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0102 (1547/152344) while in subpopulation NFE AF= 0.0166 (1132/68026). AF 95% confidence interval is 0.0158. There are 10 homozygotes in gnomad4. There are 738 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC34A3	NM_001177316.2	c.86-120C>T		intron_variant		ENST00000673835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC34A3	ENST00000673835.1	c.86-120C>T		intron_variant			NM_001177316.2	P1

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1551 AN: 152226 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.00256

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00807

Gnomad FIN AF: 0.00386

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.0119

GnomAD4 exome AF: 0.0138 AC: 14026 AN: 1017232 Hom.: 131 Cov.: 14 AF XY: 0.0137 AC XY: 7168 AN XY: 525130

Gnomad4 AFR exome AF: 0.00221

Gnomad4 AMR exome AF: 0.00528

Gnomad4 ASJ exome AF: 0.0304

Gnomad4 EAS exome AF: 0.0000265

Gnomad4 SAS exome AF: 0.00821

Gnomad4 FIN exome AF: 0.00506

Gnomad4 NFE exome AF: 0.0162

Gnomad4 OTH exome AF: 0.0137

GnomAD4 genome AF: 0.0102 AC: 1547 AN: 152344 Hom.: 10 Cov.: 33 AF XY: 0.00991 AC XY: 738 AN XY: 74486

Gnomad4 AFR AF: 0.00255

Gnomad4 AMR AF: 0.00496

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00766

Gnomad4 FIN AF: 0.00386

Gnomad4 NFE AF: 0.0166

Gnomad4 OTH AF: 0.0113

Alfa AF: 0.0144 Hom.: 3

Bravo AF: 0.00972

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs112695368; hg19: chr9-140126404;