10-100154922-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The NM_006459.4(ERLIN1):c.763C>T(p.Arg255*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,600 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 (★).
Frequency
Consequence
NM_006459.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ERLIN1 | ENST00000421367.7 | c.763C>T | p.Arg255* | stop_gained | Exon 10 of 11 | 1 | NM_006459.4 | ENSP00000410964.2 | ||
ERLIN1 | ENST00000407654.7 | c.763C>T | p.Arg255* | stop_gained | Exon 11 of 12 | 1 | ENSP00000384900.3 | |||
ERLIN1 | ENST00000370408.2 | c.763C>T | p.Arg255* | stop_gained | Exon 11 of 11 | 5 | ENSP00000359436.2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152106Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251070Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135690
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461494Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727034
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152106Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74286
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 62 Pathogenic:1Uncertain:1
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. ClinVar contains an entry for this variant (Variation ID: 226426). This premature translational stop signal has been observed in individuals with hereditary spastic paraplegia (PMID: 24482476; Invitae). This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Arg255*) in the ERLIN1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in ERLIN1 cause disease. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at