rs3812036

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003052.5(SLC34A1):c.389-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,614,098 control chromosomes in the GnomAD database, including 48,103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3656 hom., cov: 32)

Exomes 𝑓: 0.24 ( 44447 hom. )

Consequence

SLC34A1
NM_003052.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.28

Publications

31 publications found

Variant links:

Genes affected

SLC34A1 (HGNC:11019): (solute carrier family 34 member 1) Enables sodium:phosphate symporter activity. Involved in several processes, including phosphate ion homeostasis; phosphate ion transport; and response to lead ion. Located in several cellular components, including apical plasma membrane; mitotic spindle; and nuclear speck. Implicated in several diseases, including Fanconi syndrome (multiple); chronic kidney disease; hereditary hypophosphatemic rickets with hypercalciuria; hypophosphatemic nephrolithiasis/osteoporosis 1; and nephrolithiasis. [provided by Alliance of Genome Resources, Apr 2022]

SLC34A1 Gene-Disease associations (from GenCC):

hypercalcemia, infantile, 2
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
hypophosphatemic nephrolithiasis/osteoporosis 1
Inheritance: AD Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
dominant hypophosphatemia with nephrolithiasis or osteoporosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
primary Fanconi syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive infantile hypercalcemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Fanconi renotubular syndrome 2
Inheritance: AR Classification: LIMITED, NO_KNOWN Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

SLC34A1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_003052.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 5-177386403-C-T is Benign according to our data. Variant chr5-177386403-C-T is described in ClinVar as Benign. ClinVar VariationId is 1168138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003052.5. 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
	SLC34A1	NM_003052.5	MANE Select	c.389-20C>T		intron	N/A	NP_003043.3
	SLC34A1	NM_001167579.2		c.389-20C>T		intron	N/A	NP_001161051.1	Q06495-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC34A1	ENST00000324417.6	TSL:1 MANE Select	c.389-20C>T	intron	N/A	ENSP00000321424.4	Q06495-1
SLC34A1	ENST00000872468.1		c.389-20C>T	intron	N/A	ENSP00000542527.1
SLC34A1	ENST00000512593.5	TSL:2	c.389-20C>T	intron	N/A	ENSP00000423022.1	Q06495-2

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30515

AN:

152128

Hom.:

3652

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0740

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.227

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.159

Gnomad SAS

AF:

0.256

Gnomad FIN

AF:

0.320

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.253

Gnomad OTH

AF:

0.209

GnomAD2 exomes

AF:

0.228

AC:

57263

AN:

251374

AF XY:

0.237

show subpopulations

Gnomad AFR exome

AF:

0.0706

Gnomad AMR exome

AF:

0.176

Gnomad ASJ exome

AF:

0.196

Gnomad EAS exome

AF:

0.153

Gnomad FIN exome

AF:

0.301

Gnomad NFE exome

AF:

0.255

Gnomad OTH exome

AF:

0.247

GnomAD4 exome

AF:

0.243

AC:

354687

AN:

1461852

Hom.:

44447

Cov.:

AF XY:

0.244

AC XY:

177600

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.0633

AC:

2120

AN:

33480

American (AMR)

AF:

0.183

AC:

8200

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

5214

AN:

26136

East Asian (EAS)

AF:

0.208

AC:

8241

AN:

39700

South Asian (SAS)

AF:

0.270

AC:

23331

AN:

86254

European-Finnish (FIN)

AF:

0.303

AC:

16180

AN:

53408

Middle Eastern (MID)

AF:

0.258

AC:

1490

AN:

5768

European-Non Finnish (NFE)

AF:

0.248

AC:

276113

AN:

1111986

Other (OTH)

AF:

0.228

AC:

13798

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

19882

39764

59647

79529

99411

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9212

18424

27636

36848

46060

<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:

0.200

AC:

30521

AN:

152246

Hom.:

3656

Cov.:

AF XY:

0.204

AC XY:

15163

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0742

AC:

3085

AN:

41570

American (AMR)

AF:

0.227

AC:

3467

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

646

AN:

3470

East Asian (EAS)

AF:

0.158

AC:

818

AN:

5172

South Asian (SAS)

AF:

0.257

AC:

1239

AN:

4826

European-Finnish (FIN)

AF:

0.320

AC:

3398

AN:

10610

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.253

AC:

17184

AN:

67972

Other (OTH)

AF:

0.208

AC:

441

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1215

2429

3644

4858

6073

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<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:

0.209

Hom.:

875

Bravo

AF:

0.187

Asia WGS

AF:

0.217

AC:

759

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Fanconi renotubular syndrome 2 (1)

Hypercalcemia, infantile, 2 (1)

Hypophosphatemic nephrolithiasis/osteoporosis 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.080

(source)

DANN

Benign

0.45

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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