rs3812036

Positions:

• chr5-177386403-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003052.5(SLC34A1):​c.389-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,614,098 control chromosomes in the GnomAD database, including 48,103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3656 hom., cov: 32)
  • Exomes 𝑓: 0.24 (44447 hom.)
• Consequence: SLC34A1 NM_003052.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.28

Genes affected

SLC34A1 (HGNC:11019): (solute carrier family 34 member 1) Enables sodium:phosphate symporter activity. Involved in several processes, including phosphate ion homeostasis; phosphate ion transport; and response to lead ion. Located in several cellular components, including apical plasma membrane; mitotic spindle; and nuclear speck. Implicated in several diseases, including Fanconi syndrome (multiple); chronic kidney disease; hereditary hypophosphatemic rickets with hypercalciuria; hypophosphatemic nephrolithiasis/osteoporosis 1; and nephrolithiasis. [provided by Alliance of Genome Resources, Apr 2022]

SLC34A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-177386403-C-T is Benign according to our data. Variant chr5-177386403-C-T is described in ClinVar as [Benign]. Clinvar id is 1168138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-177386403-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC34A1	NM_003052.5	c.389-20C>T		intron_variant		ENST00000324417.6	NP_003043.3
SLC34A1	NM_001167579.2	c.389-20C>T		intron_variant			NP_001161051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC34A1	ENST00000324417.6	c.389-20C>T		intron_variant		1	NM_003052.5	ENSP00000321424.4
SLC34A1	ENST00000512593.5	c.389-20C>T		intron_variant		2		ENSP00000423022.1
SLC34A1	ENST00000507685.5	n.473-20C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30515 AN: 152128 Hom.: 3652 Cov.: 32

Gnomad AFR AF: 0.0740

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.209

GnomAD3 exomes AF: 0.228 AC: 57263 AN: 251374 Hom.: 7124 AF XY: 0.237 AC XY: 32235 AN XY: 135876

Gnomad AFR exome AF: 0.0706

Gnomad AMR exome AF: 0.176

Gnomad ASJ exome AF: 0.196

Gnomad EAS exome AF: 0.153

Gnomad SAS exome AF: 0.270

Gnomad FIN exome AF: 0.301

Gnomad NFE exome AF: 0.255

Gnomad OTH exome AF: 0.247

GnomAD4 exome AF: 0.243 AC: 354687 AN: 1461852 Hom.: 44447 Cov.: 51 AF XY: 0.244 AC XY: 177600 AN XY: 727230

Gnomad4 AFR exome AF: 0.0633

Gnomad4 AMR exome AF: 0.183

Gnomad4 ASJ exome AF: 0.199

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.270

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.248

Gnomad4 OTH exome AF: 0.228

GnomAD4 genome AF: 0.200 AC: 30521 AN: 152246 Hom.: 3656 Cov.: 32 AF XY: 0.204 AC XY: 15163 AN XY: 74434

Gnomad4 AFR AF: 0.0742

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.208

Alfa AF: 0.209 Hom.: 875

Bravo AF: 0.187

Asia WGS AF: 0.217 AC: 759 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	- -

Fanconi renotubular syndrome 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Hypophosphatemic nephrolithiasis/osteoporosis 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Hypercalcemia, infantile, 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.080
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3812036; hg19: chr5-176813404; COSMIC: COSV60996578; COSMIC: COSV60996578;