Variant NM_182978.4:c.-41T>C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182978.4(GNAL):c.-41T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,033,504 control chromosomes in the GnomAD database, including 41,303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 12875 hom., cov: 33)

Exomes 𝑓: 0.24 ( 28428 hom. )

Consequence

GNAL
NM_182978.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.774

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]

GNAL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 18-11689523-T-C is Benign according to our data. Variant chr18-11689523-T-C is described in ClinVar as [Benign]. Clinvar id is 1246973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAL	NM_182978.4 link	c.-41T>C		5_prime_UTR_variant	Exon 1 of 12	ENST00000334049.11	NP_892023.1	P38405-2
GNAL	XM_006722324.4 link	c.-41T>C		5_prime_UTR_variant	Exon 1 of 6		XP_006722387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAL	ENST00000334049 link	c.-41T>C		5_prime_UTR_variant	Exon 1 of 12	1	NM_182978.4	ENSP00000334051.5		P38405-2

Frequencies

GnomAD3 genomes

AF:

0.349

AC:

53023

AN:

151806

Hom.:

12838

Cov.:

show subpopulations

Gnomad AFR

AF:

0.691

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.227

Gnomad ASJ

AF:

0.283

Gnomad EAS

AF:

0.0231

Gnomad SAS

AF:

0.181

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.341

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.333

GnomAD3 exomes

AF:

0.258

AC:

AN:

318

Hom.:

AF XY:

0.308

AC XY:

AN XY:

182

show subpopulations

Gnomad SAS exome

AF:

0.500

Gnomad NFE exome

AF:

0.263

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.238

AC:

209505

AN:

881590

Hom.:

28428

Cov.:

AF XY:

0.237

AC XY:

99977

AN XY:

422180

show subpopulations

Gnomad4 AFR exome

AF:

0.706

Gnomad4 AMR exome

AF:

0.195

Gnomad4 ASJ exome

AF:

0.280

Gnomad4 EAS exome

AF:

0.0330

Gnomad4 SAS exome

AF:

0.184

Gnomad4 FIN exome

AF:

0.171

Gnomad4 NFE exome

AF:

0.235

Gnomad4 OTH exome

AF:

0.250

GnomAD4 genome

AF:

0.350

AC:

53101

AN:

151914

Hom.:

12875

Cov.:

AF XY:

0.341

AC XY:

25321

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.691

Gnomad4 AMR

AF:

0.226

Gnomad4 ASJ

AF:

0.283

Gnomad4 EAS

AF:

0.0232

Gnomad4 SAS

AF:

0.180

Gnomad4 FIN

AF:

0.166

Gnomad4 NFE

AF:

0.239

Gnomad4 OTH

AF:

0.330

Alfa

AF:

0.123

Hom.:

198

Bravo

AF:

0.367

Asia WGS

AF:

0.116

AC:

399

AN:

3418

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Jul 31, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 26% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 24. Only high quality variants are reported. -

Dystonia 25

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.2

DANN

Benign

0.64

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over