rs28542318

Positions:

• chr9-137236154-A-G
• chr9-137236154-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001177316.2(SLC34A3):​c.1538A>G​(p.Glu513Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E513V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SLC34A3 NM_001177316.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.115400106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC34A3	NM_001177316.2	c.1538A>G	p.Glu513Gly	missense_variant	13/13	ENST00000673835.1	NP_001170787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC34A3	ENST00000673835.1	c.1538A>G	p.Glu513Gly	missense_variant	13/13		NM_001177316.2	ENSP00000501114	P1
SLC34A3	ENST00000361134.2	c.1538A>G	p.Glu513Gly	missense_variant	13/13	2		ENSP00000355353	P1
SLC34A3	ENST00000538474.5	c.1538A>G	p.Glu513Gly	missense_variant	13/13	5		ENSP00000442397	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 82

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.55
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.74	T;.
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.53	N;N
REVEL	Benign	0.11
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.0010	B;B
Vest4		0.16
MutPred		0.24		Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);
MVP		0.12
MPC		0.044
ClinPred		0.90	D
GERP RS		4.2
Varity_R		0.049
gMVP		0.54

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: rs28542318; hg19: chr9-140130606;