chr6-25776649-G-A
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
NM_005495.3 missense
Scores
1
6
8
Clinical Significance
Conservation
PhyloP100: 0.660
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]
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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 | 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 | c.1042G>A | p.Gly348Arg | missense_variant | 9/12 | 1 | NM_005495.3 | P1 | |
SLC17A4 | ENST00000439485.6 | c.880G>A | p.Gly294Arg | missense_variant | 10/13 | 5 | |||
SLC17A4 | ENST00000397076.2 | c.352G>A | p.Gly118Arg | missense_variant | 5/7 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000987 AC: 15AN: 152032Hom.: 1 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000678 AC: 17AN: 250766Hom.: 0 AF XY: 0.0000517 AC XY: 7AN XY: 135496
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GnomAD4 exome AF: 0.000207 AC: 302AN: 1461582Hom.: 0 Cov.: 30 AF XY: 0.000195 AC XY: 142AN XY: 727100
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GnomAD4 genome ? AF: 0.0000987 AC: 15AN: 152032Hom.: 1 Cov.: 32 AF XY: 0.0000943 AC XY: 7AN XY: 74248
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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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
REVEL
Uncertain
Sift4G
Uncertain
D;D;D
Polyphen
0.99
.;D;.
Vest4
MutPred
0.88
.;Gain of MoRF binding (P = 0.0408);.;
MVP
MPC
0.45
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at