11-119024909-TTCAC-T
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001164278.2(SLC37A4):c.1353_1356delGTGA(p.Glu451fs) variant causes a frameshift, stop lost change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,240 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001164278.2 frameshift, stop_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC37A4 | NM_001164278.2 | c.1353_1356delGTGA | p.Glu451fs | frameshift_variant, stop_lost | Exon 12 of 12 | NP_001157750.1 | ||
SLC37A4 | NM_001164277.2 | c.1287_1290delGTGA | p.Glu429fs | frameshift_variant, stop_lost | Exon 11 of 11 | NP_001157749.1 | ||
SLC37A4 | NM_001164280.2 | c.1287_1290delGTGA | p.Glu429fs | frameshift_variant, stop_lost | Exon 9 of 9 | NP_001157752.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152240Hom.: 0 Cov.: 33
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152240Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74376
ClinVar
Submissions by phenotype
Glucose-6-phosphate transport defect Pathogenic:3Uncertain:1
disease causing -
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The frameshift c.1287_1290del(p.Ter430GlufsTer53) variant in SLC37A4 gene has been reported previously in heterozygous state in an individual affected with glycogen storage disorders (Kumar TV, et. al., 2022). The p.Ter430GlufsTer53 variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Uncertain Significance/ Pathogenic. Due to frameshift change, the sequence of a stop codon is changed to specify an amino acid Glutamic Acid instead and translation will continue until another stop codon is found at position Ter53. Loss of function variants have been previously reported to be disease causing. However since this variant is present in the last exon, functional studies will be required to prove protein truncation. Hence the variant is classified as Likely Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at