rs2328894

Variant names:

• chr6-25777954-C-T
• rs2328894
• NM_005495.3:c.1297C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_005495.3(SLC17A4):​c.1297C>T​(p.Gln433*) 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. Variant has been reported in ClinVar as Benign (★). 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: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0200
• Publications: 12 publications found

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:10929): (solute carrier family 17 member 1) Predicted to enable sialic acid transmembrane transporter activity. Involved in urate metabolic process and urate transport. Located in apical plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 6-25777954-C-T is Benign according to our data. Variant chr6-25777954-C-T is described in ClinVar as Benign. ClinVar VariationId is 3904789.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005495.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC17A4	NM_005495.3	MANE Select	c.1297C>T	p.Gln433*	stop_gained	Exon 11 of 12	NP_005486.1	Q9Y2C5-1
	SLC17A4	NM_001286121.1		c.1135C>T	p.Gln379*	stop_gained	Exon 12 of 13	NP_001273050.1	Q9Y2C5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC17A4	ENST00000377905.9	TSL:1 MANE Select	c.1297C>T	p.Gln433*	stop_gained	Exon 11 of 12	ENSP00000367137.4	Q9Y2C5-1
	SLC17A4	ENST00000867588.1		c.1297C>T	p.Gln433*	stop_gained	Exon 11 of 12	ENSP00000537647.1
	SLC17A4	ENST00000867590.1		c.1297C>T	p.Gln433*	stop_gained	Exon 11 of 12	ENSP00000537649.1

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

GnomAD2 exomes AF: 0.0106 AC: 2659 AN: 250646 AF XY: 0.0107

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 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

African (AFR) AF: 0.00215 AC: 72 AN: 33440

American (AMR) AF: 0.00470 AC: 210 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00597 AC: 156 AN: 26114

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39684

South Asian (SAS) AF: 0.00335 AC: 289 AN: 86234

European-Finnish (FIN) AF: 0.0260 AC: 1378 AN: 52972

Middle Eastern (MID) AF: 0.0118 AC: 68 AN: 5760

European-Non Finnish (NFE) AF: 0.0143 AC: 15941 AN: 1111444

Other (OTH) AF: 0.0105 AC: 636 AN: 60350

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

African (AFR) AF: 0.00253 AC: 105 AN: 41554

American (AMR) AF: 0.00530 AC: 81 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00606 AC: 21 AN: 3468

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4826

European-Finnish (FIN) AF: 0.0268 AC: 284 AN: 10606

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0140 AC: 950 AN: 67992

Other (OTH) AF: 0.00758 AC: 16 AN: 2112

Alfa AF: 0.0115 Hom.: 54

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-0.020
Vest4		0.12
GERP RS		0.72
Mutation Taster		=178/22	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs2328894; hg19: chr6-25778182;