chr14-93721541-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_178013.4(PRIMA1):c.365C>T(p.Pro122Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,611,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P122S) has been classified as Uncertain significance.
Frequency
Consequence
NM_178013.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRIMA1 | NM_178013.4 | c.365C>T | p.Pro122Leu | missense_variant | 5/5 | ENST00000393140.6 | |
PRIMA1 | XM_011536456.3 | c.365C>T | p.Pro122Leu | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRIMA1 | ENST00000393140.6 | c.365C>T | p.Pro122Leu | missense_variant | 5/5 | 1 | NM_178013.4 | P1 | |
PRIMA1 | ENST00000393143.5 | c.365C>T | p.Pro122Leu | missense_variant | 4/4 | 1 | P1 | ||
PRIMA1 | ENST00000316227.3 | c.*161C>T | 3_prime_UTR_variant | 5/5 | 1 | ||||
PRIMA1 | ENST00000477603.5 | c.*161C>T | 3_prime_UTR_variant, NMD_transcript_variant | 6/6 | 1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152070Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250362Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135370
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1459646Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726304
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152070Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74280
ClinVar
Submissions by phenotype
Sleep-related hypermotor epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 122 of the PRIMA1 protein (p.Pro122Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with PRIMA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1019024). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at