5-177390635-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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	c.936+2263A>G		intron_variant	Intron 8 of 12	ENST00000324417.6	NP_003043.3
SLC34A1	NM_001167579.2	c.*910A>G		downstream_gene_variant			NP_001161051.1

Ensembl

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

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

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.409

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.280

Gnomad4 OTH exome AF: 0.185

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

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.285

Alfa AF: 0.318 Hom.: 8481

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
DANN	Benign	0.64

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

LitVar

Other links and lift over

dbSNP: rs6420094; hg19: chr5-176817636;