rs752084146

Variant names:

• chr9-137231750-C-A
• rs752084146
• NM_001177316.2:c.48C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-137231750-C-A
• chr9-137231750-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001177316.2(SLC34A3):​c.48C>A​(p.Asp16Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D16D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SLC34A3 NM_001177316.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.285
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08597684).

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.48C>A	p.Asp16Glu	missense	Exon 2 of 13	NP_001170787.2	Q8N130
	SLC34A3	NM_001177317.2		c.48C>A	p.Asp16Glu	missense	Exon 2 of 13	NP_001170788.2	Q8N130
	SLC34A3	NM_080877.3		c.48C>A	p.Asp16Glu	missense	Exon 2 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.48C>A	p.Asp16Glu	missense	Exon 2 of 13	ENSP00000501114.1	Q8N130
	SLC34A3	ENST00000361134.2	TSL:2	c.48C>A	p.Asp16Glu	missense	Exon 2 of 13	ENSP00000355353.2	Q8N130
	SLC34A3	ENST00000538474.5	TSL:5	c.48C>A	p.Asp16Glu	missense	Exon 2 of 13	ENSP00000442397.1	Q8N130

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460932 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 726748

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111968

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.2
DANN	Benign	0.87
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M
PhyloP100		0.28
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.23	N
REVEL	Benign	0.098
Sift	Benign	0.34	T
Sift4G	Benign	0.18	T
Polyphen		0.74	P
Vest4		0.24
MutPred		0.17		Loss of phosphorylation at T14 (P = 0.195)
MVP		0.23
MPC		0.27
ClinPred		0.14	T
GERP RS		-1.8
Varity_R		0.041
gMVP		0.23
Mutation Taster		=96/4	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: rs752084146; hg19: chr9-140126202;