rs2328894

chr6-25777954-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4 BS2

The NM_005495.3(SLC17A4):c.1297C>T(p.Gln433Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,612,930 control chromosomes in the GnomAD database, including 175 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0097 (11 hom., cov: 31)
  • Exomes 𝑓: 0.013 (164 hom.)
• Consequence: SLC17A4 NM_005495.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200

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 Likely_benign. Variant got -2 ACMG points.

• PM4: Stoplost variant in NM_005495.3 Downstream stopcodon found after 522 codons.
• BS2: High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC17A4	NM_005495.3	c.1297C>T	p.Gln433Ter	stop_gained	11/12	ENST00000377905.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC17A4	ENST00000377905.9	c.1297C>T	p.Gln433Ter	stop_gained	11/12	1	NM_005495.3	P1
SLC17A4	ENST00000439485.6	c.1135C>T	p.Gln379Ter	stop_gained	12/13	5
SLC17A4	ENST00000397076.2	c.*854C>T		3_prime_UTR_variant	6/7	2

Frequencies

GnomAD3 genomes AF: 0.00970 AC: 1476 AN: 152118 Hom.: 11 Cov.: 31

Gnomad AFR AF: 0.00253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00531

Gnomad ASJ AF: 0.00606

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.0268

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.00766

GnomAD3 exomes AF: 0.0106 AC: 2659 AN: 250646 Hom.: 30 AF XY: 0.0107 AC XY: 1445 AN XY: 135508

Gnomad AFR exome AF: 0.00234

Gnomad AMR exome AF: 0.00466

Gnomad ASJ exome AF: 0.00566

Gnomad EAS exome AF: 0.000326

Gnomad SAS exome AF: 0.00330

Gnomad FIN exome AF: 0.0246

Gnomad NFE exome AF: 0.0150

Gnomad OTH exome AF: 0.0106

GnomAD4 exome AF: 0.0128 AC: 18759 AN: 1460694 Hom.: 164 Cov.: 31 AF XY: 0.0127 AC XY: 9194 AN XY: 726670

Gnomad4 AFR exome AF: 0.00215

Gnomad4 AMR exome AF: 0.00470

Gnomad4 ASJ exome AF: 0.00597

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.00335

Gnomad4 FIN exome AF: 0.0260

Gnomad4 NFE exome AF: 0.0143

Gnomad4 OTH exome AF: 0.0105

GnomAD4 genome AF: 0.00970 AC: 1476 AN: 152236 Hom.: 11 Cov.: 31 AF XY: 0.00998 AC XY: 743 AN XY: 74448

Gnomad4 AFR AF: 0.00253

Gnomad4 AMR AF: 0.00530

Gnomad4 ASJ AF: 0.00606

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.0268

Gnomad4 NFE AF: 0.0140

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.0123 Hom.: 38

Bravo AF: 0.00759

TwinsUK AF: 0.0135 AC: 50

ALSPAC AF: 0.0171 AC: 66

ESP6500AA AF: 0.00431 AC: 19

ESP6500EA AF: 0.0117 AC: 101

ExAC AF: 0.0109 AC: 1326

Asia WGS AF: 0.00404 AC: 14 AN: 3476

EpiCase AF: 0.0108

EpiControl AF: 0.0124

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Pathogenic	0.27
Cadd	Pathogenic	36
Dann	Benign	0.97
Eigen	Uncertain	0.21
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.040	N
MutationTaster	Benign	1.0	A;A;N
Vest4		0.12
GERP RS		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.20		Position offset: -28

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2328894; hg19: chr6-25778182;