13-114325385-TGG-CTC

Variant names:

• chr13-114325385-TGG-CTC
• NM_032436.4:c.1543_1545delTGGinsCTC
• CHAMP1 p.Trp515Leu

Variant summary

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

The NM_032436.4(CHAMP1):​c.1543_1545delTGGinsCTC​(p.Trp515Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHAMP1 NM_032436.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31
• Publications: 0 publications found

Genes affected

CHAMP1 (HGNC:20311): (chromosome alignment maintaining phosphoprotein 1) This gene encodes a zinc finger protein that functions as a regulator of chromosome segregation in mitosis. The encoded protein is required for correct alignment of chromosomes on the metaphase plate, and plays a role in maintaining the attachment of sister kinetochores to microtubules from opposite spindle poles. Mutations in this gene are associated with an autosomal dominant form of intellectual disability. [provided by RefSeq, Jul 2017]

CHAMP1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• intellectual disability, autosomal dominant 40

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• autosomal dominant non-syndromic intellectual disability

  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_032436.4. 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
	CHAMP1	NM_032436.4	MANE Select	c.1543_1545delTGGinsCTC	p.Trp515Leu	missense	N/A	NP_115812.1	Q96JM3
	CHAMP1	NM_001164144.3		c.1543_1545delTGGinsCTC	p.Trp515Leu	missense	N/A	NP_001157616.1	Q96JM3
	CHAMP1	NM_001164145.3		c.1543_1545delTGGinsCTC	p.Trp515Leu	missense	N/A	NP_001157617.1	Q96JM3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHAMP1	ENST00000361283.4	TSL:1 MANE Select	c.1543_1545delTGGinsCTC	p.Trp515Leu	missense	N/A	ENSP00000354730.1	Q96JM3
	CHAMP1	ENST00000643483.2		c.1543_1545delTGGinsCTC	p.Trp515Leu	missense	N/A	ENSP00000496699.1	Q96JM3
	CHAMP1	ENST00000644294.2		c.1543_1545delTGGinsCTC	p.Trp515Leu	missense	N/A	ENSP00000495985.2	Q96JM3

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		2.3

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: chr13-115090860;