rs537620020
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001171613.2(PREPL):āc.1850T>Cā(p.Leu617Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000694 in 1,613,062 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L617V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001171613.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PREPL | NM_001171613.2 | c.1850T>C | p.Leu617Pro | missense_variant | 14/14 | ENST00000409411.6 | |
SLC3A1 | NM_000341.4 | c.*784A>G | 3_prime_UTR_variant | 10/10 | ENST00000260649.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PREPL | ENST00000409411.6 | c.1850T>C | p.Leu617Pro | missense_variant | 14/14 | 1 | NM_001171613.2 | P4 | |
SLC3A1 | ENST00000260649.11 | c.*784A>G | 3_prime_UTR_variant | 10/10 | 1 | NM_000341.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000132 AC: 33AN: 250638Hom.: 1 AF XY: 0.000184 AC XY: 25AN XY: 135526
GnomAD4 exome AF: 0.0000719 AC: 105AN: 1460742Hom.: 1 Cov.: 30 AF XY: 0.000105 AC XY: 76AN XY: 726696
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152320Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74486
ClinVar
Submissions by phenotype
Myasthenic syndrome, congenital, 22 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 23, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 706 of the PREPL protein (p.Leu706Pro). This variant is present in population databases (rs537620020, gnomAD 0.1%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with PREPL-related conditions. ClinVar contains an entry for this variant (Variation ID: 575325). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 02, 2023 | The c.2117T>C (p.L706P) alteration is located in exon 14 (coding exon 14) of the PREPL gene. This alteration results from a T to C substitution at nucleotide position 2117, causing the leucine (L) at amino acid position 706 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at