rs398122924
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1PP5
The NM_182978.4(GNAL):c.1109C>A(p.Ser370Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
GNAL
NM_182978.4 stop_gained
NM_182978.4 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 7.50
Genes affected
GNAL (HGNC:4388): (G protein subunit alpha L) This gene encodes a stimulatory G protein alpha subunit which mediates odorant signaling in the olfactory epithelium. This protein couples dopamine type 1 receptors and adenosine A2A receptors and is widely expressed in the central nervous system. Mutations in this gene have been associated with dystonia 25 and this gene is located in a susceptibility region for bipolar disorder and schizophrenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant 18-11872345-C-A is Pathogenic according to our data. Variant chr18-11872345-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 39968.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNAL | NM_182978.4 | c.1109C>A | p.Ser370Ter | stop_gained | 10/12 | ENST00000334049.11 | |
GNAL | NM_001369387.1 | c.878C>A | p.Ser293Ter | stop_gained | 10/12 | ENST00000423027.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNAL | ENST00000334049.11 | c.1109C>A | p.Ser370Ter | stop_gained | 10/12 | 1 | NM_182978.4 | ||
GNAL | ENST00000423027.8 | c.878C>A | p.Ser293Ter | stop_gained | 10/12 | 1 | NM_001369387.1 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1418088Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0AN XY: 706272
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
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0
AN:
1418088
Hom.:
Cov.:
26
AF XY:
AC XY:
0
AN XY:
706272
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Dystonia 25 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A;A;A
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at