chr18-11689600-G-A

Variant names:

• chr18-11689600-G-A
• rs1032625784
• NM_182978.4:c.37G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182978.4(GNAL):​c.37G>A​(p.Gly13Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000846 in 1,182,702 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: GNAL NM_182978.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.29

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAL	NM_182978.4	c.37G>A	p.Gly13Arg	missense_variant	Exon 1 of 12	ENST00000334049.11	NP_892023.1
GNAL	XM_006722324.4	c.37G>A	p.Gly13Arg	missense_variant	Exon 1 of 6		XP_006722387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAL	ENST00000334049.11	c.37G>A	p.Gly13Arg	missense_variant	Exon 1 of 12	1	NM_182978.4	ENSP00000334051.5
GNAL	ENST00000585590.1	n.-90G>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.46e-7 AC: 1 AN: 1182702 Hom.: 0 Cov.: 30 AF XY: 0.00000174 AC XY: 1 AN XY: 573370

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000376

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	23
DANN	Uncertain	1.0
Eigen	Benign	-0.089
Eigen_PC	Benign	-0.031
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.56	T
M_CAP	Pathogenic	0.98	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.36	T
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.42
MutPred		0.18		Loss of relative solvent accessibility (P = 0.0676);
MVP		0.58
MPC		2.6
ClinPred		0.99	D
GERP RS		2.8
gMVP		0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1032625784; hg19: chr18-11689599;