9-137234192-G-C

Variant names:

• chr9-137234192-G-C
• NM_001177316.2:c.1009G>C

Variant summary

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

The NM_001177316.2(SLC34A3):​c.1009G>C​(p.Gly337Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,756 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G337S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC34A3 NM_001177316.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13

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=0.1609239).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC34A3	NM_001177316.2	c.1009G>C	p.Gly337Arg	missense_variant	Exon 10 of 13	ENST00000673835.1	NP_001170787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC34A3	ENST00000673835.1	c.1009G>C	p.Gly337Arg	missense_variant	Exon 10 of 13		NM_001177316.2	ENSP00000501114.1
SLC34A3	ENST00000361134.2	c.1009G>C	p.Gly337Arg	missense_variant	Exon 10 of 13	2		ENSP00000355353.2
SLC34A3	ENST00000538474.5	c.1009G>C	p.Gly337Arg	missense_variant	Exon 10 of 13	5		ENSP00000442397.1
SLC34A3	ENST00000673865.1	c.1009G>C	p.Gly337Arg	missense_variant	Exon 10 of 10			ENSP00000501101.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453756 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 722872

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	5.1
DANN	Benign	0.93
DEOGEN2	Benign	0.39	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.063	N
LIST_S2	Uncertain	0.94	D;.
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.47	N;N
REVEL	Benign	0.12
Sift	Benign	0.13	T;T
Sift4G	Benign	0.062	T;T
Polyphen		0.53	P;P
Vest4		0.32
MutPred		0.59		Gain of MoRF binding (P = 0.019);Gain of MoRF binding (P = 0.019);
MVP		0.17
MPC		0.068
ClinPred		0.16	T
GERP RS		-7.2
Varity_R		0.083
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-140128644;