chr18-11689920-G-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2
The NM_182978.4(GNAL):c.357G>T(p.Thr119=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000624 in 1,427,222 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 Benign (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000063 ( 0 hom. )
Consequence
GNAL
NM_182978.4 synonymous
NM_182978.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.536
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
?
Variant 18-11689920-G-T is Benign according to our data. Variant chr18-11689920-G-T is described in ClinVar as [Benign]. Clinvar id is 526219.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.536 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0000634 (81/1276964) while in subpopulation MID AF= 0.000402 (2/4974). AF 95% confidence interval is 0.0000709. There are 0 homozygotes in gnomad4_exome. There are 41 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAd at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNAL | NM_182978.4 | c.357G>T | p.Thr119= | synonymous_variant | 1/12 | ENST00000334049.11 | |
GNAL | XM_006722324.4 | c.357G>T | p.Thr119= | synonymous_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNAL | ENST00000334049.11 | c.357G>T | p.Thr119= | synonymous_variant | 1/12 | 1 | NM_182978.4 | ||
GNAL | ENST00000585590.1 | n.231G>T | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000532 AC: 8AN: 150258Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
8
AN:
150258
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000228 AC: 15AN: 65708Hom.: 0 AF XY: 0.000162 AC XY: 6AN XY: 36946
GnomAD3 exomes
AF:
AC:
15
AN:
65708
Hom.:
AF XY:
AC XY:
6
AN XY:
36946
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000634 AC: 81AN: 1276964Hom.: 0 Cov.: 31 AF XY: 0.0000657 AC XY: 41AN XY: 623760
GnomAD4 exome
AF:
AC:
81
AN:
1276964
Hom.:
Cov.:
31
AF XY:
AC XY:
41
AN XY:
623760
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000532 AC: 8AN: 150258Hom.: 0 Cov.: 33 AF XY: 0.0000681 AC XY: 5AN XY: 73470
GnomAD4 genome
?
AF:
AC:
8
AN:
150258
Hom.:
Cov.:
33
AF XY:
AC XY:
5
AN XY:
73470
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Dystonic disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 22, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at