chr16-31484743-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_003041.4(SLC5A2):c.197C>T(p.Pro66Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000112 in 1,610,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
SLC5A2
NM_003041.4 missense, splice_region
NM_003041.4 missense, splice_region
Scores
5
9
5
Splicing: ADA: 0.9983
2
Clinical Significance
Conservation
PhyloP100: 4.80
Genes affected
SLC5A2 (HGNC:11037): (solute carrier family 5 member 2) This gene encodes a member of the sodium glucose cotransporter family which are sodium-dependent glucose transport proteins. The encoded protein is the major cotransporter involved in glucose reabsorption in the kidney. Mutations in this gene are associated with renal glucosuria. Two transcript variants, one protein-coding and one not, have been found for this gene. [provided by RefSeq, Feb 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC5A2 | NM_003041.4 | c.197C>T | p.Pro66Leu | missense_variant, splice_region_variant | 2/14 | ENST00000330498.4 | |
SLC5A2 | XM_006721072.5 | c.197C>T | p.Pro66Leu | missense_variant, splice_region_variant | 2/13 | ||
SLC5A2 | XM_024450402.2 | c.197C>T | p.Pro66Leu | missense_variant, splice_region_variant | 2/11 | ||
SLC5A2 | NR_130783.2 | n.211C>T | splice_region_variant, non_coding_transcript_exon_variant | 2/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC5A2 | ENST00000330498.4 | c.197C>T | p.Pro66Leu | missense_variant, splice_region_variant | 2/14 | 1 | NM_003041.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152204Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248562Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134650
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GnomAD4 exome AF: 0.0000110 AC: 16AN: 1458204Hom.: 0 Cov.: 32 AF XY: 0.00000827 AC XY: 6AN XY: 725614
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74358
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Familial renal glucosuria Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | MVZ Medizinische Genetik Mainz | Nov 08, 2021 | PM2_SUP, PP3, PP4 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
.;M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Benign
T;T
Sift4G
Uncertain
D;T
Polyphen
1.0
.;D
Vest4
0.58
MutPred
0.67
.;Gain of MoRF binding (P = 0.0456);
MVP
MPC
0.57
ClinPred
D
GERP RS
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Splicing
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Calibrated prediction
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at