rs9358890

chr6-25779164-A-Gchr6-25779164-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005495.3(SLC17A4):c.1470A>G(p.Lys490=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 1,613,766 control chromosomes in the GnomAD database, including 12,323 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 0.077 (1152 hom., cov: 32)
  • Exomes 𝑓: 0.074 (11171 hom.)
• Consequence: SLC17A4 NM_005495.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382

Genes affected

SLC17A4 (HGNC:10932): (solute carrier family 17 member 4) Phosphate homeostasis is maintained by regulating intake, intestinal absorption, bone deposition and resorption, and renal excretion of phosphate. The central molecule in the control of phosphate excretion from the kidney is the sodium/phosphate cotransporter NPT1 (SLC17A1; MIM 182308), which is located in the renal proximal tubule. NPT1 uses the transmembrane electrochemical potential gradient of sodium to transport phosphate across the cell membrane. SLC17A4 is a similar sodium/phosphate cotransporter in the intestinal mucosa that plays an important role in the absorption of phosphate from the intestine (summary by Shibui et al., 1999 [PubMed 10319585]).[supplied by OMIM, Feb 2011]

SLC17A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-0.382 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC17A4	NM_005495.3	c.1470A>G	p.Lys490=	synonymous_variant	12/12	ENST00000377905.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC17A4	ENST00000377905.9	c.1470A>G	p.Lys490=	synonymous_variant	12/12	1	NM_005495.3	P1
SLC17A4	ENST00000439485.6	c.1308A>G	p.Lys436=	synonymous_variant	13/13	5
SLC17A4	ENST00000397076.2	c.*1027A>G		3_prime_UTR_variant	7/7	2

Frequencies

GnomAD3 genomes AF: 0.0771 AC: 11732 AN: 152130 Hom.: 1146 Cov.: 32

Gnomad AFR AF: 0.0480

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0570

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.0302

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0460

Gnomad OTH AF: 0.0915

GnomAD3 exomes AF: 0.125 AC: 31443 AN: 251124 Hom.: 4328 AF XY: 0.121 AC XY: 16390 AN XY: 135702

Gnomad AFR exome AF: 0.0483

Gnomad AMR exome AF: 0.253

Gnomad ASJ exome AF: 0.0593

Gnomad EAS exome AF: 0.501

Gnomad SAS exome AF: 0.184

Gnomad FIN exome AF: 0.0321

Gnomad NFE exome AF: 0.0457

Gnomad OTH exome AF: 0.0943

GnomAD4 exome AF: 0.0745 AC: 108883 AN: 1461516 Hom.: 11171 Cov.: 31 AF XY: 0.0771 AC XY: 56030 AN XY: 727040

Gnomad4 AFR exome AF: 0.0465

Gnomad4 AMR exome AF: 0.243

Gnomad4 ASJ exome AF: 0.0601

Gnomad4 EAS exome AF: 0.565

Gnomad4 SAS exome AF: 0.180

Gnomad4 FIN exome AF: 0.0319

Gnomad4 NFE exome AF: 0.0446

Gnomad4 OTH exome AF: 0.0856

GnomAD4 genome AF: 0.0772 AC: 11748 AN: 152250 Hom.: 1152 Cov.: 32 AF XY: 0.0833 AC XY: 6204 AN XY: 74442

Gnomad4 AFR AF: 0.0479

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.0570

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.0302

Gnomad4 NFE AF: 0.0460

Gnomad4 OTH AF: 0.0943

Alfa AF: 0.0623 Hom.: 525

Bravo AF: 0.0866

Asia WGS AF: 0.307 AC: 1065 AN: 3478

EpiCase AF: 0.0540

EpiControl AF: 0.0483

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	5.7
Dann	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs9358890; hg19: chr6-25779392; COSMIC: COSV55082588; COSMIC: COSV55082588;