chr4-26386369-CCT-GCA

Variant names:

• chr4-26386369-CCT-GCA
• NM_015874.6:c.37_39delCCTinsGCA
• RBPJ p.Pro13Ala

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015874.6(RBPJ):​c.37_39delCCTinsGCA​(p.Pro13Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBPJ NM_015874.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.86
• Publications: 0 publications found

Genes affected

RBPJ (HGNC:5724): (recombination signal binding protein for immunoglobulin kappa J region) The protein encoded by this gene is a transcriptional regulator important in the Notch signaling pathway. The encoded protein acts as a repressor when not bound to Notch proteins and an activator when bound to Notch proteins. It is thought to function by recruiting chromatin remodeling complexes containing histone deacetylase or histone acetylase proteins to Notch signaling pathway genes. Several transcript variants encoding different isoforms have been found for this gene, and several pseudogenes of this gene exist on chromosome 9. [provided by RefSeq, Oct 2013]

RBPJ Gene-Disease associations (from GenCC):

• Adams-Oliver syndrome 3

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Adams-Oliver syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015874.6. 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
	RBPJ	NM_015874.6	MANE Select	c.37_39delCCTinsGCA	p.Pro13Ala	missense	N/A	NP_056958.3
	RBPJ	NM_001374400.1		c.76_78delCCTinsGCA	p.Pro26Ala	missense	N/A	NP_001361329.1	Q06330-1
	RBPJ	NM_005349.4		c.76_78delCCTinsGCA	p.Pro26Ala	missense	N/A	NP_005340.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBPJ	ENST00000355476.8	TSL:1 MANE Select	c.37_39delCCTinsGCA	p.Pro13Ala	missense	N/A	ENSP00000347659.4	Q06330-7
	RBPJ	ENST00000361572.10	TSL:1	c.76_78delCCTinsGCA	p.Pro26Ala	missense	N/A	ENSP00000354528.6	Q06330-1
	RBPJ	ENST00000342320.8	TSL:1	c.34_36delCCTinsGCA	p.Pro12Ala	missense	N/A	ENSP00000340124.4	Q06330-6

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-26387991;