Variant 6-25776649-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005495.3(SLC17A4):c.1042G>A(p.Gly348Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000196 in 1,613,614 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

SLC17A4
NM_005495.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.660

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:):

SLC17A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC17A4	NM_005495.3 linkuse as main transcript	c.1042G>A	p.Gly348Arg	missense_variant	9/12	ENST00000377905.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC17A4	ENST00000377905.9 linkuse as main transcript	c.1042G>A	p.Gly348Arg	missense_variant	9/12	1	NM_005495.3	P1	Q9Y2C5-1
SLC17A4	ENST00000439485.6 linkuse as main transcript	c.880G>A	p.Gly294Arg	missense_variant	10/13	5			Q9Y2C5-2
SLC17A4	ENST00000397076.2 linkuse as main transcript	c.352G>A	p.Gly118Arg	missense_variant	5/7	2			Q9Y2C5-4

Frequencies

GnomAD3 genomes

AF:

0.0000987

AC:

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000678

AC:

AN:

250766

Hom.:

AF XY:

0.0000517

AC XY:

AN XY:

135496

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000207

AC:

302

AN:

1461582

Hom.:

Cov.:

AF XY:

0.000195

AC XY:

142

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000255

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.0000987

AC:

AN:

152032

Hom.:

Cov.:

AF XY:

0.0000943

AC XY:

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000210

Hom.:

Bravo

AF:

0.0000869

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2022

The c.1042G>A (p.G348R) alteration is located in exon 9 (coding exon 8) of the SLC17A4 gene. This alteration results from a G to A substitution at nucleotide position 1042, causing the glycine (G) at amino acid position 348 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Benign

-0.035

BayesDel_noAF

Uncertain

-0.050

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.089

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.79

T;T;T

M_CAP

Benign

0.074

MetaRNN

Uncertain

0.55

D;D;D

MetaSVM

Benign

-0.69

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.43

REVEL

Uncertain

0.29

Sift4G

Uncertain

0.022

D;D;D

Polyphen

0.99

.;D;.

Vest4

0.64

MutPred

0.88

.;Gain of MoRF binding (P = 0.0408);.;

MVP

0.71

MPC

0.45

ClinPred

0.67

GERP RS

3.8

Varity_R

0.94

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over