13-114325333-A-C

Variant names:

• chr13-114325333-A-C
• NM_032436.4:c.1491A>C
• CHAMP1 p.Arg497Arg

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_032436.4(CHAMP1):​c.1491A>C​(p.Arg497Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=1.06 with no splicing effect.

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.1491A>C	p.Arg497Arg	synonymous	Exon 3 of 3	NP_115812.1	Q96JM3
	CHAMP1	NM_001164144.3		c.1491A>C	p.Arg497Arg	synonymous	Exon 3 of 3	NP_001157616.1	Q96JM3
	CHAMP1	NM_001164145.3		c.1491A>C	p.Arg497Arg	synonymous	Exon 3 of 3	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.1491A>C	p.Arg497Arg	synonymous	Exon 3 of 3	ENSP00000354730.1	Q96JM3
	CHAMP1	ENST00000643483.2		c.1491A>C	p.Arg497Arg	synonymous	Exon 3 of 3	ENSP00000496699.1	Q96JM3
	CHAMP1	ENST00000644294.2		c.1491A>C	p.Arg497Arg	synonymous	Exon 3 of 3	ENSP00000495985.2	Q96JM3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.3
DANN	Benign	0.79
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

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

Other links and lift over

hg19: chr13-115090808;