rs5030873

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003052.5(SLC34A1):c.774T>C(p.His258His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,613,864 control chromosomes in the GnomAD database, including 79,348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5971 hom., cov: 32)

Exomes 𝑓: 0.31 ( 73377 hom. )

Consequence

SLC34A1
NM_003052.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -3.89

Publications

21 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
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
hypophosphatemic nephrolithiasis/osteoporosis 1
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
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

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 5-177388123-T-C is Benign according to our data. Variant chr5-177388123-T-C is described in ClinVar as Benign. ClinVar VariationId is 352965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.89 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC34A1	NM_003052.5 link	c.774T>C	p.His258His	synonymous_variant	Exon 7 of 13	ENST00000324417.6	NP_003043.3	Q06495-1A0A024R7R9Q86VN6Q7Z725
SLC34A1	NM_001167579.2 link	c.774T>C	p.His258His	synonymous_variant	Exon 7 of 9		NP_001161051.1	Q06495-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC34A1	ENST00000324417.6 link	c.774T>C	p.His258His	synonymous_variant	Exon 7 of 13	1	NM_003052.5	ENSP00000321424.4	Q06495-1
SLC34A1	ENST00000512593.5 link	c.774T>C	p.His258His	synonymous_variant	Exon 7 of 9	2		ENSP00000423022.1	Q06495-2
SLC34A1	ENST00000507685.5 link	n.978T>C		non_coding_transcript_exon_variant	Exon 6 of 10	2

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38256

AN:

151972

Hom.:

5972

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0740

Gnomad AMI

AF:

0.264

Gnomad AMR

AF:

0.258

Gnomad ASJ

AF:

0.305

Gnomad EAS

AF:

0.225

Gnomad SAS

AF:

0.352

Gnomad FIN

AF:

0.432

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.322

Gnomad OTH

AF:

0.259

GnomAD2 exomes

AF:

0.295

AC:

74017

AN:

251256

AF XY:

0.309

show subpopulations

Gnomad AFR exome

AF:

0.0684

Gnomad AMR exome

AF:

0.202

Gnomad ASJ exome

AF:

0.308

Gnomad EAS exome

AF:

0.224

Gnomad FIN exome

AF:

0.409

Gnomad NFE exome

AF:

0.323

Gnomad OTH exome

AF:

0.315

GnomAD4 exome

AF:

0.311

AC:

454998

AN:

1461774

Hom.:

73377

Cov.:

AF XY:

0.314

AC XY:

228476

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.0631

AC:

2113

AN:

33480

American (AMR)

AF:

0.210

AC:

9385

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

8077

AN:

26134

East Asian (EAS)

AF:

0.271

AC:

10772

AN:

39700

South Asian (SAS)

AF:

0.367

AC:

31666

AN:

86256

European-Finnish (FIN)

AF:

0.405

AC:

21598

AN:

53358

Middle Eastern (MID)

AF:

0.351

AC:

2023

AN:

5766

European-Non Finnish (NFE)

AF:

0.316

AC:

351547

AN:

1111966

Other (OTH)

AF:

0.295

AC:

17817

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

20524

41047

61571

82094

102618

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11288

22576

33864

45152

56440

<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:

0.252

AC:

38256

AN:

152090

Hom.:

5971

Cov.:

AF XY:

0.258

AC XY:

19159

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.0742

AC:

3080

AN:

41510

American (AMR)

AF:

0.257

AC:

3937

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.305

AC:

1060

AN:

3470

East Asian (EAS)

AF:

0.224

AC:

1160

AN:

5172

South Asian (SAS)

AF:

0.352

AC:

1700

AN:

4824

European-Finnish (FIN)

AF:

0.432

AC:

4571

AN:

10576

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.322

AC:

21856

AN:

67934

Other (OTH)

AF:

0.260

AC:

548

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

1432

2864

4295

5727

7159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.287

Hom.:

3925

Bravo

AF:

0.229

Asia WGS

AF:

0.290

AC:

1013

AN:

3478

EpiCase

AF:

0.325

EpiControl

AF:

0.328

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 21, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.His258His in exon 7 of SLC34A1: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 41.15% (2715/6598) of Finnish chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs5030873). -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Hypophosphatemic nephrolithiasis/osteoporosis 1

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 16, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fanconi renotubular syndrome 2

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hypercalcemia, infantile, 2

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.028

(source)

DANN

Benign

0.35

PhyloP100

-3.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over