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: 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
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369387.1. 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_001369387.1	MANE Plus Clinical	c.113_118delCTTACA	p.Ala38_Lys40delinsGlu	disruptive_inframe_deletion	Exon 1 of 12	NP_001356316.1	A8K1Y9
	GNAL	NM_182978.4	MANE Select	c.377-307_377-302delCTTACA		intron	N/A	NP_892023.1	P38405-2
	GNAL	NM_001142339.3		c.113_118delCTTACA	p.Ala38_Lys40delinsGlu	disruptive_inframe_deletion	Exon 2 of 13	NP_001135811.1	A8K1Y9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAL	ENST00000423027.8	TSL:1 MANE Plus Clinical	c.113_118delCTTACA	p.Ala38_Lys40delinsGlu	disruptive_inframe_deletion	Exon 1 of 12	ENSP00000408489.2	P38405-1
	GNAL	ENST00000535121.5	TSL:1	c.113_118delCTTACA	p.Ala38_Lys40delinsGlu	disruptive_inframe_deletion	Exon 2 of 13	ENSP00000439023.1	P38405-1
	GNAL	ENST00000334049.11	TSL:1 MANE Select	c.377-307_377-302delCTTACA		intron	N/A	ENSP00000334051.5	P38405-2

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Dystonic disorder (1)

Computational scores

Source: dbNSFP v4.9

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;