NM_003052.5:c.936+2263A>G

Variant names:

• chr5-177390635-A-G
• rs6420094
• NM_003052.5:c.936+2263A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.332
• Publications: 61 publications found

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)

ACMG classification

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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC34A1	NM_003052.5	MANE Select	c.936+2263A>G		intron	N/A	NP_003043.3
	SLC34A1	NM_001167579.2		c.*910A>G		downstream_gene	N/A	NP_001161051.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC34A1	ENST00000324417.6	TSL:1 MANE Select	c.936+2263A>G		intron	N/A	ENSP00000321424.4
	SLC34A1	ENST00000507685.5	TSL:2	n.1227+2263A>G		intron	N/A
	SLC34A1	ENST00000513614.1	TSL:2	n.838+151A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.291 AC: 43940 AN: 151254 Hom.: 6792 Cov.: 30

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.: 41 AF XY: 0.267 AC XY: 146 AN XY: 546

African (AFR) AF: 0.111 AC: 2 AN: 18

American (AMR) AF: 0.00 AC: 0 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 9 AN: 22

East Asian (EAS) AF: 0.183 AC: 11 AN: 60

South Asian (SAS) AF: 0.500 AC: 3 AN: 6

European-Finnish (FIN) AF: 0.173 AC: 9 AN: 52

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.280 AC: 236 AN: 842

Other (OTH) AF: 0.185 AC: 10 AN: 54

GnomAD4 genome AF: 0.290 AC: 43965 AN: 151374 Hom.: 6801 Cov.: 30 AF XY: 0.296 AC XY: 21831 AN XY: 73878

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.4
DANN	Benign	0.64
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6420094; hg19: chr5-176817636;