6-25770433-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The ENST00000377905.9(SLC17A4):c.581C>T(p.Pro194Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000185 in 1,613,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 0 hom. )
Consequence
SLC17A4
ENST00000377905.9 missense
ENST00000377905.9 missense
Scores
5
7
7
Clinical Significance
Conservation
PhyloP100: 3.73
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 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.825
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC17A4 | NM_005495.3 | c.581C>T | p.Pro194Leu | missense_variant | 5/12 | ENST00000377905.9 | NP_005486.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC17A4 | ENST00000377905.9 | c.581C>T | p.Pro194Leu | missense_variant | 5/12 | 1 | NM_005495.3 | ENSP00000367137 | P1 | |
SLC17A4 | ENST00000439485.6 | c.419C>T | p.Pro140Leu | missense_variant | 6/13 | 5 | ENSP00000391345 | |||
SLC17A4 | ENST00000397076.2 | c.135+1243C>T | intron_variant | 2 | ENSP00000380266 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152188Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000956 AC: 24AN: 251154Hom.: 0 AF XY: 0.0000958 AC XY: 13AN XY: 135740
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GnomAD4 exome AF: 0.000192 AC: 280AN: 1461808Hom.: 0 Cov.: 34 AF XY: 0.000197 AC XY: 143AN XY: 727216
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GnomAD4 genome AF: 0.000118 AC: 18AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74344
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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 | Jul 19, 2023 | The c.581C>T (p.P194L) alteration is located in exon 5 (coding exon 4) of the SLC17A4 gene. This alteration results from a C to T substitution at nucleotide position 581, causing the proline (P) at amino acid position 194 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
.;M
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
.;D
REVEL
Uncertain
Sift
Pathogenic
.;D
Sift4G
Pathogenic
D;D
Polyphen
0.97
.;D
Vest4
MVP
MPC
0.43
ClinPred
D
GERP RS
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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