Menu
GeneBe

18-11689920-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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.536
Variant links:
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
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.536 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GNALNM_182978.4 linkuse as main transcriptc.357G>T p.Thr119= synonymous_variant 1/12 ENST00000334049.11
GNALXM_006722324.4 linkuse as main transcriptc.357G>T p.Thr119= synonymous_variant 1/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GNALENST00000334049.11 linkuse as main transcriptc.357G>T p.Thr119= synonymous_variant 1/121 NM_182978.4 P38405-2
GNALENST00000585590.1 linkuse as main transcriptn.231G>T non_coding_transcript_exon_variant 1/22

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000532
AC:
8
AN:
150258
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000251
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000578
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000736
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000228
AC:
15
AN:
65708
Hom.:
0
AF XY:
0.000162
AC XY:
6
AN XY:
36946
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000715
Gnomad ASJ exome
AF:
0.00220
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000852
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000815
Gnomad OTH exome
AF:
0.000557
GnomAD4 exome
AF:
0.0000634
AC:
81
AN:
1276964
Hom.:
0
Cov.:
31
AF XY:
0.0000657
AC XY:
41
AN XY:
623760
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000392
Gnomad4 ASJ exome
AF:
0.00156
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000154
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000363
Gnomad4 OTH exome
AF:
0.000133
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000532
AC:
8
AN:
150258
Hom.:
0
Cov.:
33
AF XY:
0.0000681
AC XY:
5
AN XY:
73470
show subpopulations
Gnomad4 AFR
AF:
0.0000251
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000578
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000736
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000125

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 submitterclinical testingInvitaeDec 22, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.39
Cadd
Benign
12
Dann
Benign
0.94

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs747999584; hg19: chr18-11689919; API