17-17793779-C-CCAGCAACAG

Variant names:

• chr17-17793779-C-CCAGCAACAG
• rs587780428
• NM_030665.4:c.836_837insACAGCAGCA

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP3

The NM_030665.4(RAI1):​c.836_837insACAGCAGCA​(p.Gln279_Gln280insGlnGlnGln) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000235 in 1,278,812 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q279Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: RAI1 NM_030665.4 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• Publications: 1 publications found

Genes affected

RAI1 (HGNC:9834): (retinoic acid induced 1) This gene is located within the Smith-Magenis syndrome region on chromosome 17. It is highly similar to its mouse counterpart and is expressed at high levels mainly in neuronal tissues. The protein encoded by this gene includes a polymorphic polyglutamine tract in the N-terminal domain. Expression of the mouse counterpart in neurons is induced by retinoic acid. This gene is associated with both the severity of the phenotype and the response to medication in schizophrenic patients. [provided by RefSeq, Jul 2008]

RAI1 Gene-Disease associations (from GenCC):

• Smith-Magenis syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet
• Potocki-Lupski syndrome

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_030665.4

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030665.4. 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
	RAI1	NM_030665.4	MANE Select	c.836_837insACAGCAGCA	p.Gln279_Gln280insGlnGlnGln	disruptive_inframe_insertion	Exon 3 of 6	NP_109590.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAI1	ENST00000353383.6	TSL:1 MANE Select	c.836_837insACAGCAGCA	p.Gln279_Gln280insGlnGlnGln	disruptive_inframe_insertion	Exon 3 of 6	ENSP00000323074.4	Q7Z5J4-1
	RAI1	ENST00000918590.1		c.836_837insACAGCAGCA	p.Gln279_Gln280insGlnGlnGln	disruptive_inframe_insertion	Exon 2 of 5	ENSP00000588649.1
	RAI1	ENST00000955422.1		c.836_837insACAGCAGCA	p.Gln279_Gln280insGlnGlnGln	disruptive_inframe_insertion	Exon 3 of 6	ENSP00000625481.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000235 AC: 3 AN: 1278812 Hom.: 0 Cov.: 38 AF XY: 0.00000158 AC XY: 1 AN XY: 632490

African (AFR) AF: 0.00 AC: 0 AN: 28608

American (AMR) AF: 0.00 AC: 0 AN: 31712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23378

East Asian (EAS) AF: 0.00 AC: 0 AN: 18624

South Asian (SAS) AF: 0.00 AC: 0 AN: 55806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46186

Middle Eastern (MID) AF: 0.000206 AC: 1 AN: 4866

European-Non Finnish (NFE) AF: 0.00000197 AC: 2 AN: 1017670

Other (OTH) AF: 0.00 AC: 0 AN: 51962

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4

Splicing

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

Other links and lift over

dbSNP: rs587780428; hg19: chr17-17697093;