rs28407527

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_001177316.2(SLC34A3):​c.757T>A​(p.Leu253Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,336 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L253L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC34A3 NM_001177316.2 missense, splice_region
• Scores: Splicing: ADA: 0.003181
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC34A3	NM_001177316.2	c.757T>A	p.Leu253Met	missense_variant, splice_region_variant	Exon 8 of 13	ENST00000673835.1	NP_001170787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC34A3	ENST00000673835.1	c.757T>A	p.Leu253Met	missense_variant, splice_region_variant	Exon 8 of 13		NM_001177316.2	ENSP00000501114.1
SLC34A3	ENST00000361134.2	c.757T>A	p.Leu253Met	missense_variant, splice_region_variant	Exon 8 of 13	2		ENSP00000355353.2
SLC34A3	ENST00000538474.5	c.757T>A	p.Leu253Met	missense_variant, splice_region_variant	Exon 8 of 13	5		ENSP00000442397.1
SLC34A3	ENST00000673865.1	c.757T>A	p.Leu253Met	missense_variant, splice_region_variant	Exon 8 of 10			ENSP00000501101.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460336 Hom.: 0 Cov.: 44 AF XY: 0.00000275 AC XY: 2 AN XY: 726508

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: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.48	T;T
Eigen	Benign	0.14
Eigen_PC	Benign	-0.039
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.75	T;.
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Benign	-0.51	T
MutationAssessor	Pathogenic	3.3	M;M
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.21
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	D;D
Vest4		0.43
MutPred		0.54		Gain of disorder (P = 0.0704);Gain of disorder (P = 0.0704);
MVP		0.40
MPC		0.28
ClinPred		0.91	D
GERP RS		2.3
Varity_R		0.15
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0032
dbscSNV1_RF	Benign	0.18
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: chr9-140128085;