rs121918239

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3BS1BS2

The NM_001177316.2(SLC34A3):c.756G>A(p.Gln252Gln) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.00232 in 1,600,354 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 14 hom. )

Consequence

SLC34A3
NM_001177316.2 splice_region, synonymous

Scores

Splicing: ADA: 0.9948

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:2U:6B:3

Conservation

PhyloP100: 3.96

Publications

8 publications found

Variant links:

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

SLC34A3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00163 (248/152236) while in subpopulation SAS AF = 0.00622 (30/4820). AF 95% confidence interval is 0.00448. There are 0 homozygotes in GnomAd4. There are 119 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 14 AR,SD gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC34A3	NM_001177316.2	MANE Select	c.756G>A	p.Gln252Gln	splice_region synonymous	Exon 7 of 13	NP_001170787.2	Q8N130
SLC34A3	NM_001177317.2		c.756G>A	p.Gln252Gln	splice_region synonymous	Exon 7 of 13	NP_001170788.2	Q8N130
SLC34A3	NM_080877.3		c.756G>A	p.Gln252Gln	splice_region synonymous	Exon 7 of 13	NP_543153.2	Q8N130

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC34A3	ENST00000673835.1	MANE Select	c.756G>A	p.Gln252Gln	splice_region synonymous	Exon 7 of 13	ENSP00000501114.1	Q8N130
SLC34A3	ENST00000361134.2	TSL:2	c.756G>A	p.Gln252Gln	splice_region synonymous	Exon 7 of 13	ENSP00000355353.2	Q8N130
SLC34A3	ENST00000538474.5	TSL:5	c.756G>A	p.Gln252Gln	splice_region synonymous	Exon 7 of 13	ENSP00000442397.1	Q8N130

Frequencies

GnomAD3 genomes

AF:

0.00162

AC:

247

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00601

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00259

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.00240

AC:

519

AN:

216202

AF XY:

0.00271

show subpopulations

Gnomad AFR exome

AF:

0.000649

Gnomad AMR exome

AF:

0.000587

Gnomad ASJ exome

AF:

0.000107

Gnomad EAS exome

AF:

0.0000611

Gnomad FIN exome

AF:

0.000239

Gnomad NFE exome

AF:

0.00277

Gnomad OTH exome

AF:

0.00239

GnomAD4 exome

AF:

0.00239

AC:

3465

AN:

1448118

Hom.:

Cov.:

AF XY:

0.00254

AC XY:

1826

AN XY:

719966

show subpopulations

African (AFR)

AF:

0.000181

AC:

AN:

33222

American (AMR)

AF:

0.000646

AC:

AN:

43368

Ashkenazi Jewish (ASJ)

AF:

0.0000771

AC:

AN:

25942

East Asian (EAS)

AF:

0.0000511

AC:

AN:

39110

South Asian (SAS)

AF:

0.00778

AC:

662

AN:

85122

European-Finnish (FIN)

AF:

0.000394

AC:

AN:

48176

Middle Eastern (MID)

AF:

0.00231

AC:

AN:

5638

European-Non Finnish (NFE)

AF:

0.00239

AC:

2646

AN:

1107730

Other (OTH)

AF:

0.00145

AC:

AN:

59810

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

222

444

667

889

1111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

200

300

400

500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00163

AC:

248

AN:

152236

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

119

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.000602

AC:

AN:

41554

American (AMR)

AF:

0.000914

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00622

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00259

AC:

176

AN:

67986

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00198

Hom.:

Bravo

AF:

0.00125

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal recessive hypophosphatemic bone disease (6)

not provided (3)

not specified (1)

SLC34A3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Benign

0.97

PhyloP100

4.0

Mutation Taster

=19/81

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.96

SpliceAI score (max)

0.65

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.65

Position offset: -36

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over