NM_182978.4:c.*1134T>A

Variant names:

• chr18-11882269-T-A
• rs602201
• NM_182978.4:c.*1134T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182978.4(GNAL):​c.*1134T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,028 control chromosomes in the GnomAD database, including 9,289 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (9289 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: GNAL NM_182978.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680
• Publications: 9 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: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAL	NM_182978.4	MANE Select	c.*1134T>A		3_prime_UTR	Exon 12 of 12	NP_892023.1
	GNAL	NM_001369387.1	MANE Plus Clinical	c.*1134T>A		3_prime_UTR	Exon 12 of 12	NP_001356316.1
	GNAL	NM_001142339.3		c.*1134T>A		3_prime_UTR	Exon 13 of 13	NP_001135811.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAL	ENST00000334049.11	TSL:1 MANE Select	c.*1134T>A		3_prime_UTR	Exon 12 of 12	ENSP00000334051.5
	GNAL	ENST00000423027.8	TSL:1 MANE Plus Clinical	c.*1134T>A		3_prime_UTR	Exon 12 of 12	ENSP00000408489.2

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51983 AN: 151910 Hom.: 9279 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.348

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.342 AC: 52007 AN: 152028 Hom.: 9289 Cov.: 32 AF XY: 0.346 AC XY: 25705 AN XY: 74298

African (AFR) AF: 0.264 AC: 10966 AN: 41480

American (AMR) AF: 0.429 AC: 6554 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1484 AN: 3466

East Asian (EAS) AF: 0.351 AC: 1810 AN: 5154

South Asian (SAS) AF: 0.455 AC: 2194 AN: 4822

European-Finnish (FIN) AF: 0.349 AC: 3688 AN: 10558

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.358 AC: 24356 AN: 67972

Other (OTH) AF: 0.342 AC: 722 AN: 2110

Alfa AF: 0.362 Hom.: 1286

Bravo AF: 0.344

Asia WGS AF: 0.391 AC: 1358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.23
DANN	Benign	0.42
PhyloP100		-0.068
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs602201; hg19: chr18-11882268;