rs782604758
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001164279.2(SLC37A4):c.126_127insG(p.Leu43AlafsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000361 in 1,605,154 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. G42G) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001164279.2 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.345_346insG | p.Leu116AlafsTer15 | frameshift_variant | 4/11 | ENST00000642844.3 | |
SLC37A4 | NM_001164279.2 | c.126_127insG | p.Leu43AlafsTer15 | frameshift_variant | 4/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC37A4 | ENST00000330775.9 | c.345_346insG | p.Leu116AlafsTer15 | frameshift_variant | 3/10 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000855 AC: 2AN: 233828Hom.: 0 AF XY: 0.0000158 AC XY: 2AN XY: 126700
GnomAD4 exome AF: 0.0000392 AC: 57AN: 1452950Hom.: 0 Cov.: 32 AF XY: 0.0000374 AC XY: 27AN XY: 721768
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74346
ClinVar
Submissions by phenotype
Glucose-6-phosphate transport defect Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jun 22, 2023 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 01, 2023 | This sequence change creates a premature translational stop signal (p.Leu116Alafs*15) 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). This variant is present in population databases (rs782604758, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with SLC37A4-related conditions. ClinVar contains an entry for this variant (Variation ID: 529223). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at