Genetic Variant SLC34A1:c.936+2263A>G (chr5-177390635-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003052.5(SLC34A1):c.936+2263A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,436 control chromosomes in the GnomAD database, including 6,842 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 6801 hom., cov: 30)

Exomes 𝑓: 0.26 ( 41 hom. )

Consequence

SLC34A1
NM_003052.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.332

Publications

61 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC34A1	NM_003052.5 link	c.936+2263A>G		intron_variant	Intron 8 of 12	ENST00000324417.6	NP_003043.3
SLC34A1	NM_001167579.2 link	c.*910A>G		downstream_gene_variant			NP_001161051.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
SLC34A1	ENST00000324417.6 link	c.936+2263A>G	intron_variant	Intron 8 of 12	1	NM_003052.5	ENSP00000321424.4
SLC34A1	ENST00000507685.5 link	n.1227+2263A>G	intron_variant	Intron 6 of 9	2
SLC34A1	ENST00000513614.1 link	n.838+151A>G	intron_variant	Intron 1 of 3	2
SLC34A1	ENST00000512593.5 link	c.*910A>G	downstream_gene_variant		2		ENSP00000423022.1

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

43940

AN:

151254

Hom.:

6792

Cov.:

show subpopulations

Gnomad AFR

AF:

0.204

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.272

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.227

Gnomad SAS

AF:

0.352

Gnomad FIN

AF:

0.431

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.323

Gnomad OTH

AF:

0.286

GnomAD4 exome

AF:

0.264

AC:

280

AN:

1062

Hom.:

AF XY:

0.267

AC XY:

146

AN XY:

546

show subpopulations

African (AFR)

AF:

0.111

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.409

AC:

AN:

East Asian (EAS)

AF:

0.183

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.173

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.280

AC:

236

AN:

842

Other (OTH)

AF:

0.185

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.290

AC:

43965

AN:

151374

Hom.:

6801

Cov.:

AF XY:

0.296

AC XY:

21831

AN XY:

73878

show subpopulations

African (AFR)

AF:

0.204

AC:

8427

AN:

41208

American (AMR)

AF:

0.272

AC:

4121

AN:

15168

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

1209

AN:

3460

East Asian (EAS)

AF:

0.226

AC:

1164

AN:

5152

South Asian (SAS)

AF:

0.353

AC:

1687

AN:

4784

European-Finnish (FIN)

AF:

0.431

AC:

4522

AN:

10484

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.323

AC:

21895

AN:

67836

Other (OTH)

AF:

0.285

AC:

594

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1465

2930

4395

5860

7325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

452

904

1356

1808

2260

<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:

0.308

Hom.:

22329

Bravo

AF:

0.274

Asia WGS

AF:

0.310

AC:

1081

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.4

(source)

DANN

Benign

0.64

PhyloP100

-0.33

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

Other links and lift over