GNAL p.Ala415Ala

Variant names:

• chr18-11881000-G-G
• NM_182978.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr18-11881001--
• chr18-11881003-C-T
• chr18-11881003-C-A
• chr18-11881003-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_182978.4(GNAL):​c. variant causes a intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GNAL NM_182978.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.52
• 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 25

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.		intron	N/A	NP_892023.1	P38405-2
	GNAL	NM_001369387.1	MANE Plus Clinical	c.		intron	N/A	NP_001356316.1	A8K1Y9
	GNAL	NM_001142339.3		c.		intron	N/A	NP_001135811.1	A8K1Y9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr18-11880999;