rs141627694
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PP3_Strong
The NM_003041.4(SLC5A2):āc.1145T>Cā(p.Met382Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000987 in 1,611,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_003041.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC5A2 | NM_003041.4 | c.1145T>C | p.Met382Thr | missense_variant | 10/14 | ENST00000330498.4 | |
SLC5A2 | XM_006721072.5 | c.1145T>C | p.Met382Thr | missense_variant | 10/13 | ||
SLC5A2 | XM_024450402.2 | c.1129+147T>C | intron_variant | ||||
SLC5A2 | NR_130783.2 | n.1143+147T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC5A2 | ENST00000330498.4 | c.1145T>C | p.Met382Thr | missense_variant | 10/14 | 1 | NM_003041.4 | P1 | |
SLC5A2 | ENST00000419665.6 | c.1129+147T>C | intron_variant, NMD_transcript_variant | 1 | |||||
SLC5A2 | ENST00000568188.1 | n.409T>C | non_coding_transcript_exon_variant | 2/3 | 2 | ||||
SLC5A2 | ENST00000568891.1 | n.281+147T>C | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152198Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000659 AC: 16AN: 242830Hom.: 0 AF XY: 0.0000754 AC XY: 10AN XY: 132634
GnomAD4 exome AF: 0.0000980 AC: 143AN: 1459000Hom.: 0 Cov.: 33 AF XY: 0.0000978 AC XY: 71AN XY: 725878
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74366
ClinVar
Submissions by phenotype
Familial renal glucosuria Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | The SLC5A2 c.1145T>C (p.Met382Thr) missense variant has been reported in one study in which it was found in a compound heterozygous state with another missense variant in one patient with severe renal glucosuria (Calado et al. 2008). Control data are unavailable for this variant which is reported at a frequency of 0.0001502 in the European (non-Finnish) population of the Exome Aggregation Consortium. The evidence for this variant is limited. The p.Met382Thr variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for renal glucosuria. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at