rs1553751196

Variant names:

• chr3-123447965-CCCGAGT-C
• rs1553751196
• NM_183357.3:c.575_580delACTCGG

Your query was ambiguous. Multiple possible variants found:

• chr3-123447965-CCCGAGT-C
• chr3-123447965-CCCGAGT-CCCGAGTCCGAGT

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_183357.3(ADCY5):​c.575_580delACTCGG​(p.Asp192_Ser193del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,313,596 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: ADCY5 NM_183357.3 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.52
• Publications: 0 publications found

Genes affected

ADCY5 (HGNC:236): (adenylate cyclase 5) This gene encodes a member of the membrane-bound adenylyl cyclase enzymes. Adenylyl cyclases mediate G protein-coupled receptor signaling through the synthesis of the second messenger cAMP. Activity of the encoded protein is stimulated by the Gs alpha subunit of G protein-coupled receptors and is inhibited by protein kinase A, calcium and Gi alpha subunits. Single nucleotide polymorphisms in this gene may be associated with low birth weight and type 2 diabetes. Alternatively spliced transcript variants that encode different isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

ADCY5 Gene-Disease associations (from GenCC):

• dyskinesia with orofacial involvement, autosomal dominant

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: G2P
• neurodevelopmental disorder with hyperkinetic movements and dyskinesia

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• familial dyskinesia and facial myokymia

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
• choreatic disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_183357.3

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY5	NM_183357.3	c.575_580delACTCGG	p.Asp192_Ser193del	disruptive_inframe_deletion	Exon 1 of 21	ENST00000462833.6	NP_899200.1
ADCY5	NM_001378259.1	c.575_580delACTCGG	p.Asp192_Ser193del	disruptive_inframe_deletion	Exon 1 of 22		NP_001365188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY5	ENST00000462833.6	c.575_580delACTCGG	p.Asp192_Ser193del	disruptive_inframe_deletion	Exon 1 of 21	1	NM_183357.3	ENSP00000419361.1
ADCY5	ENST00000850916.1	c.737_742delACTCGG	p.Asp246_Ser247del	disruptive_inframe_deletion	Exon 1 of 21			ENSP00000520999.1
ADCY5	ENST00000699718.1	c.575_580delACTCGG	p.Asp192_Ser193del	disruptive_inframe_deletion	Exon 1 of 22			ENSP00000514543.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000685 AC: 9 AN: 1313596 Hom.: 0 AF XY: 0.00000467 AC XY: 3 AN XY: 643072

African (AFR) AF: 0.00 AC: 0 AN: 27716

American (AMR) AF: 0.00 AC: 0 AN: 24278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20338

East Asian (EAS) AF: 0.00 AC: 0 AN: 32046

South Asian (SAS) AF: 0.0000151 AC: 1 AN: 66172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43664

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5208

European-Non Finnish (NFE) AF: 0.00000769 AC: 8 AN: 1040230

Other (OTH) AF: 0.00 AC: 0 AN: 53944

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5

Splicing

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

Other links and lift over

dbSNP: rs1553751196; hg19: chr3-123166812;