19-4155001-G-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_032607.3(CREB3L3):c.130G>T(p.Glu44*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,420 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 Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_032607.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CREB3L3 | NM_032607.3 | c.130G>T | p.Glu44* | stop_gained | 2/10 | ENST00000078445.7 | NP_115996.1 | |
CREB3L3 | NM_001271995.2 | c.130G>T | p.Glu44* | stop_gained | 2/10 | NP_001258924.1 | ||
CREB3L3 | NM_001271996.2 | c.130G>T | p.Glu44* | stop_gained | 2/10 | NP_001258925.1 | ||
CREB3L3 | NM_001271997.2 | c.130G>T | p.Glu44* | stop_gained | 2/9 | NP_001258926.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CREB3L3 | ENST00000078445.7 | c.130G>T | p.Glu44* | stop_gained | 2/10 | 1 | NM_032607.3 | ENSP00000078445.1 | ||
CREB3L3 | ENST00000595923.5 | c.130G>T | p.Glu44* | stop_gained | 2/10 | 1 | ENSP00000469355.1 | |||
CREB3L3 | ENST00000602257.5 | c.130G>T | p.Glu44* | stop_gained | 2/10 | 1 | ENSP00000472399.1 | |||
CREB3L3 | ENST00000602147.1 | c.130G>T | p.Glu44* | stop_gained | 2/9 | 1 | ENSP00000470119.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1458420Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 725636
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 02, 2022 | This sequence change creates a premature translational stop signal (p.Glu44*) in the CREB3L3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CREB3L3 are known to be pathogenic (PMID: 21666694, 26427795). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CREB3L3-related conditions. 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
Publications
No publications associated with this variant yet.