dbSNP rs2328894: SLC17A4:p.Gln433* (chr6-25777954-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0200

Publications

12 publications found

Variant links:

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]

SLC17A4 links:

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]

SLC17A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A4	NM_005495.3 link	c.1297C>T	p.Gln433*	stop_gained	Exon 11 of 12	ENST00000377905.9	NP_005486.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SLC17A4	ENST00000377905.9 link	c.1297C>T	p.Gln433*	stop_gained	Exon 11 of 12	1	NM_005495.3	ENSP00000367137.4
SLC17A4	ENST00000439485.6 link	c.1135C>T	p.Gln379*	stop_gained	Exon 12 of 13	5		ENSP00000391345.3
SLC17A4	ENST00000397076.2 link	c.*854C>T		3_prime_UTR_variant	Exon 6 of 7	2		ENSP00000380266.2

Frequencies

GnomAD3 genomes

AF:

0.00970

AC:

1476

AN:

152118

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0127

AC XY:

9194

AN XY:

726670

show subpopulations

African (AFR)

AF:

0.00215

AC:

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:

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:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0143

AC:

15941

AN:

1111444

Other (OTH)

AF:

0.0105

AC:

636

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

848

1697

2545

3394

4242

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

572

1144

1716

2288

2860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00970

AC:

1476

AN:

152236

Hom.:

Cov.:

AF XY:

0.00998

AC XY:

743

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.00253

AC:

105

AN:

41554

American (AMR)

AF:

0.00530

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00606

AC:

AN:

3468

East Asian (EAS)

AF:

0.000772

AC:

AN:

5184

South Asian (SAS)

AF:

0.00249

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0268

AC:

284

AN:

10606

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0140

AC:

950

AN:

67992

Other (OTH)

AF:

0.00758

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

160

239

319

399

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0115

Hom.:

Bravo

AF:

0.00759

TwinsUK

AF:

0.0135

AC:

ALSPAC

AF:

0.0171

AC:

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.0117

AC:

101

ExAC

AF:

0.0109

AC:

1326

Asia WGS

AF:

0.00404

AC:

AN:

3476

EpiCase

AF:

0.0108

EpiControl

AF:

0.0124

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SLC17A4: BS1, BS2

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0

.;.

Eigen

Uncertain

0.21

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.0

.;.

MetaRNN

Benign

0.0

.;.

MutationAssessor

Benign

0.0

.;.

PhyloP100

-0.020

PROVEAN

Benign

0.0

.;.

REVEL

Benign

0.0

Sift

Pathogenic

0.0

.;.

Sift4G

Pathogenic

0.0

.;.

Vest4

0.12

GERP RS

0.72

Mutation Taster

=178/22

disease causing (fs/PTC)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over