rs987117042
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Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7
The NM_182978.4(GNAL):c.69G>A(p.Ser23Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000292 in 1,369,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000016 ( 0 hom. )
Consequence
GNAL
NM_182978.4 synonymous
NM_182978.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.12
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_benign. Variant got -1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP7
Synonymous conserved (PhyloP=1.12 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GNAL | NM_182978.4 | c.69G>A | p.Ser23Ser | synonymous_variant | 1/12 | ENST00000334049.11 | NP_892023.1 | |
GNAL | XM_006722324.4 | c.69G>A | p.Ser23Ser | synonymous_variant | 1/6 | XP_006722387.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GNAL | ENST00000334049.11 | c.69G>A | p.Ser23Ser | synonymous_variant | 1/12 | 1 | NM_182978.4 | ENSP00000334051.5 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151822Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000164 AC: 2AN: 1217366Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 594686
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 151822Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74158
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Dystonic disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 06, 2017 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with GNAL-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change affects codon 23 of the GNAL mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the GNAL protein. The GNAL gene has multiple clinically relevant transcripts. The c.69G>A variant occurs in the alternate transcript NM_182978.3, which corresponds to position c.-62177G>A in NM_001142339.2, the primary transcript listed in the Methods. - |
Computational scores
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at