rs1474282972
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The ENST00000330775.9(SLC37A4):c.595del(p.Leu199TrpfsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,628 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. L199L) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
ENST00000330775.9 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC37A4 | NM_001164277.2 | c.595del | p.Leu199TrpfsTer13 | frameshift_variant | 6/11 | ENST00000642844.3 | |
SLC37A4 | NM_001164279.2 | c.376del | p.Leu126TrpfsTer13 | frameshift_variant | 6/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC37A4 | ENST00000330775.9 | c.595del | p.Leu199TrpfsTer13 | frameshift_variant | 5/10 | 5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 249064Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135138
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461628Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727100
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Glucose-6-phosphate transport defect Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 13, 2023 | This sequence change creates a premature translational stop signal (p.Leu199Trpfs*13) in the SLC37A4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC37A4 are known to be pathogenic (PMID: 9758626, 10940311). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 552905). This premature translational stop signal has been observed in individual(s) with a glycogen storage disease (PMID: 22899091). This variant is present in population databases (no rsID available, gnomAD 0.006%). - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jul 17, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at