chr13-114324473-GC-G

Position:

• chr13-114324473-GC-G

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The ENST00000361283.4(CHAMP1):​c.635del​(p.Pro212LeufsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHAMP1 ENST00000361283.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: -0.00400

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]

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 38 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 13-114324473-GC-G is Pathogenic according to our data. Variant chr13-114324473-GC-G is described in ClinVar as [Pathogenic]. Clinvar id is 208414.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-114324473-GC-G is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHAMP1	NM_032436.4	c.635del	p.Pro212LeufsTer7	frameshift_variant	3/3	ENST00000361283.4	NP_115812.1
CHAMP1	NM_001164144.3	c.635del	p.Pro212LeufsTer7	frameshift_variant	3/3		NP_001157616.1
CHAMP1	NM_001164145.3	c.635del	p.Pro212LeufsTer7	frameshift_variant	3/3		NP_001157617.1
CHAMP1	XM_047430277.1	c.635del	p.Pro212LeufsTer7	frameshift_variant	3/3		XP_047286233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHAMP1	ENST00000361283.4	c.635del	p.Pro212LeufsTer7	frameshift_variant	3/3	1	NM_032436.4	ENSP00000354730	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, autosomal dominant 40 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 03, 2015

- -

intellectual disability with severe speech impairment Pathogenic:1

Pathogenic, criteria provided, single submitter

research

Institute of Human Genetics, University Medical Center Hamburg-Eppendorf

Aug 13, 2015

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs797044961; hg19: chr13-115089948;