rs28407527

Variant names:

• chr9-137233633-T-C
• rs28407527
• NM_001177316.2:c.757T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-137233633-T-C
• chr9-137233633-T-A
• chr9-137233633-T-G

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.757T>C​(p.Leu253Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 1,610,930 control chromosomes in the GnomAD database, including 151,484 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14178 hom., cov: 32)
  • Exomes 𝑓: 0.43 (137306 hom.)
• Consequence: SLC34A3 NM_001177316.2 splice_region, synonymous
• Scores: Splicing: ADA: 0.003826
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 1.80
• Publications: 18 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: AR, SD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 9-137233633-T-C is Benign according to our data. Variant chr9-137233633-T-C is described in ClinVar as Benign. ClinVar VariationId is 281214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.8 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.549 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.757T>C	p.Leu253Leu	splice_region synonymous	Exon 8 of 13	NP_001170787.2	Q8N130
	SLC34A3	NM_001177317.2		c.757T>C	p.Leu253Leu	splice_region synonymous	Exon 8 of 13	NP_001170788.2	Q8N130
	SLC34A3	NM_080877.3		c.757T>C	p.Leu253Leu	splice_region synonymous	Exon 8 of 13	NP_543153.2	Q8N130

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC34A3	ENST00000673835.1	MANE Select	c.757T>C	p.Leu253Leu	splice_region synonymous	Exon 8 of 13	ENSP00000501114.1	Q8N130
	SLC34A3	ENST00000361134.2	TSL:2	c.757T>C	p.Leu253Leu	splice_region synonymous	Exon 8 of 13	ENSP00000355353.2	Q8N130
	SLC34A3	ENST00000538474.5	TSL:5	c.757T>C	p.Leu253Leu	splice_region synonymous	Exon 8 of 13	ENSP00000442397.1	Q8N130

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64956 AN: 151728 Hom.: 14173 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.474

GnomAD2 exomes AF: 0.451 AC: 113088 AN: 250510 AF XY: 0.447

Gnomad AFR exome AF: 0.400

Gnomad AMR exome AF: 0.620

Gnomad ASJ exome AF: 0.441

Gnomad EAS exome AF: 0.487

Gnomad FIN exome AF: 0.361

Gnomad NFE exome AF: 0.415

Gnomad OTH exome AF: 0.441

GnomAD4 exome AF: 0.431 AC: 628292 AN: 1459084 Hom.: 137306 Cov.: 44 AF XY: 0.431 AC XY: 312768 AN XY: 725978

African (AFR) AF: 0.405 AC: 13556 AN: 33446

American (AMR) AF: 0.614 AC: 27431 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 11471 AN: 26124

East Asian (EAS) AF: 0.504 AC: 19997 AN: 39688

South Asian (SAS) AF: 0.468 AC: 40367 AN: 86234

European-Finnish (FIN) AF: 0.366 AC: 19109 AN: 52228

Middle Eastern (MID) AF: 0.468 AC: 2685 AN: 5742

European-Non Finnish (NFE) AF: 0.420 AC: 466718 AN: 1110574

Other (OTH) AF: 0.447 AC: 26958 AN: 60340

GnomAD4 genome AF: 0.428 AC: 64987 AN: 151846 Hom.: 14178 Cov.: 32 AF XY: 0.433 AC XY: 32124 AN XY: 74202

African (AFR) AF: 0.402 AC: 16655 AN: 41404

American (AMR) AF: 0.559 AC: 8532 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1520 AN: 3466

East Asian (EAS) AF: 0.492 AC: 2523 AN: 5124

South Asian (SAS) AF: 0.486 AC: 2344 AN: 4826

European-Finnish (FIN) AF: 0.362 AC: 3820 AN: 10564

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.414 AC: 28128 AN: 67890

Other (OTH) AF: 0.472 AC: 995 AN: 2108

Alfa AF: 0.426 Hom.: 48285

Bravo AF: 0.443

Asia WGS AF: 0.471 AC: 1642 AN: 3478

EpiCase AF: 0.429

EpiControl AF: 0.430

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)
-	-	4	not specified (4)
-	-	1	Autosomal recessive hypophosphatemic bone disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Benign	0.65
PhyloP100		1.8
Mutation Taster		=52/48	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0038
dbscSNV1_RF	Benign	0.62
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: rs28407527; hg19: chr9-140128085; COSMIC: COSV63186438; COSMIC: COSV63186438;