rs890228437
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7
The NM_182978.4(GNAL):c.249C>A(p.Ala83Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000026 in 1,537,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A83A) has been classified as Uncertain significance.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000022 ( 0 hom. )
Consequence
GNAL
NM_182978.4 synonymous
NM_182978.4 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.95
Publications
0 publications found
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]
GNAL Gene-Disease associations (from GenCC):
- dystonia 25Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.19).
BP7
Synonymous conserved (PhyloP=-1.95 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_182978.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GNAL | NM_182978.4 | MANE Select | c.249C>A | p.Ala83Ala | synonymous | Exon 1 of 12 | NP_892023.1 | P38405-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GNAL | ENST00000334049.11 | TSL:1 MANE Select | c.249C>A | p.Ala83Ala | synonymous | Exon 1 of 12 | ENSP00000334051.5 | P38405-2 | |
| GNAL | ENST00000585590.1 | TSL:2 | n.123C>A | non_coding_transcript_exon | Exon 1 of 2 |
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 152022Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152022
Hom.:
Cov.:
33
Gnomad AFR
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GnomAD2 exomes AF: 0.00000720 AC: 1AN: 138834 AF XY: 0.0000129 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
138834
AF XY:
Gnomad AFR exome
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GnomAD4 exome AF: 0.00000217 AC: 3AN: 1385042Hom.: 0 Cov.: 32 AF XY: 0.00000438 AC XY: 3AN XY: 685084 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
3
AN:
1385042
Hom.:
Cov.:
32
AF XY:
AC XY:
3
AN XY:
685084
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
29096
American (AMR)
AF:
AC:
0
AN:
35978
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24542
East Asian (EAS)
AF:
AC:
0
AN:
33058
South Asian (SAS)
AF:
AC:
1
AN:
78228
European-Finnish (FIN)
AF:
AC:
0
AN:
44048
Middle Eastern (MID)
AF:
AC:
0
AN:
5640
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1076966
Other (OTH)
AF:
AC:
0
AN:
57486
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000343967), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.392
Heterozygous variant carriers
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2
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome 0.00000658 AC: 1AN: 152022Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74254 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152022
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
74254
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41422
American (AMR)
AF:
AC:
0
AN:
15254
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5180
South Asian (SAS)
AF:
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
AC:
0
AN:
10564
Middle Eastern (MID)
AF:
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67986
Other (OTH)
AF:
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
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0.95
Allele balance
Age Distribution
Genome Het
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Alfa
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Bravo
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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