rs1060504720

Variant names:

• chr18-11752545-GCTTACA-G
• rs1060504720
• NM_001369387.1:c.113_118delCTTACA

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 5P and 2B. PM2 PM4 PP3 BP6_Moderate

The NM_001369387.1(GNAL):​c.113_118delCTTACA​(p.Ala38_Lys40delinsGlu) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GNAL NM_001369387.1 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 8.59
• 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: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001369387.1.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• BP6: Variant 18-11752545-GCTTACA-G is Benign according to our data. Variant chr18-11752545-GCTTACA-G is described in ClinVar as Benign. ClinVar VariationId is 416014.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAL	NM_001369387.1	c.113_118delCTTACA	p.Ala38_Lys40delinsGlu	disruptive_inframe_deletion	Exon 1 of 12	ENST00000423027.8	NP_001356316.1
GNAL	NM_182978.4	c.377-307_377-302delCTTACA		intron_variant	Intron 1 of 11	ENST00000334049.11	NP_892023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAL	ENST00000423027.8	c.113_118delCTTACA	p.Ala38_Lys40delinsGlu	disruptive_inframe_deletion	Exon 1 of 12	1	NM_001369387.1	ENSP00000408489.2
GNAL	ENST00000535121.5	c.113_118delCTTACA	p.Ala38_Lys40delinsGlu	disruptive_inframe_deletion	Exon 2 of 13	1		ENSP00000439023.1
GNAL	ENST00000334049.11	c.377-307_377-302delCTTACA		intron_variant	Intron 1 of 11	1	NM_182978.4	ENSP00000334051.5
GNAL	ENST00000269162.9	c.113_118delCTTACA	p.Ala38_Lys40delinsGlu	disruptive_inframe_deletion	Exon 2 of 13	2		ENSP00000269162.4

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dystonic disorder Benign:1

Oct 08, 2016

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.6
Mutation Taster		=47/153	disease causing

Splicing

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

Other links and lift over

dbSNP: rs1060504720; hg19: chr18-11752544;