Genetic Variant CHAMP1:p.Trp515Leu (chr13-114325386-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032436.4(CHAMP1):c.1544G>T(p.Trp515Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CHAMP1
NM_032436.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.48

Publications

0 publications found

Variant links:

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

CHAMP1 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19131044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CHAMP1	NM_032436.4 link	c.1544G>T	p.Trp515Leu	missense_variant	Exon 3 of 3	ENST00000361283.4	NP_115812.1
CHAMP1	NM_001164144.3 link	c.1544G>T	p.Trp515Leu	missense_variant	Exon 3 of 3		NP_001157616.1
CHAMP1	NM_001164145.3 link	c.1544G>T	p.Trp515Leu	missense_variant	Exon 3 of 3		NP_001157617.1
CHAMP1	XM_047430277.1 link	c.1544G>T	p.Trp515Leu	missense_variant	Exon 3 of 3		XP_047286233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHAMP1	ENST00000361283.4 link	c.1544G>T	p.Trp515Leu	missense_variant	Exon 3 of 3	1	NM_032436.4	ENSP00000354730.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

T;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.0

.;T

M_CAP

Benign

0.0077

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.2

M;M

PhyloP100

1.5

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.97

N;.

REVEL

Benign

0.083

Sift

Benign

0.26

T;.

Sift4G

Benign

0.67

T;.

Vest4

0.38

ClinPred

0.59

GERP RS

5.8

Varity_R

0.13

gMVP

0.17

Mutation Taster

=91/9

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over