NM_032436.4:c.755C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_032436.4(CHAMP1):c.755C>T(p.Ala252Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00036 in 1,614,182 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 2 hom. )

Consequence

CHAMP1
NM_032436.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.93

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055391192).

BP6

Variant 13-114324597-C-T is Benign according to our data. Variant chr13-114324597-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 445741.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 340 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHAMP1	NM_032436.4 link	c.755C>T	p.Ala252Val	missense_variant	Exon 3 of 3	ENST00000361283.4	NP_115812.1	Q96JM3
CHAMP1	NM_001164144.3 link	c.755C>T	p.Ala252Val	missense_variant	Exon 3 of 3		NP_001157616.1	Q96JM3
CHAMP1	NM_001164145.3 link	c.755C>T	p.Ala252Val	missense_variant	Exon 3 of 3		NP_001157617.1	Q96JM3
CHAMP1	XM_047430277.1 link	c.755C>T	p.Ala252Val	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.755C>T	p.Ala252Val	missense_variant	Exon 3 of 3	1	NM_032436.4	ENSP00000354730.1		Q96JM3

Frequencies

GnomAD3 genomes

AF:

0.00223

AC:

339

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00799

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000545

AC:

137

AN:

251370

Hom.:

AF XY:

0.000412

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00828

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000165

AC:

241

AN:

1461878

Hom.:

Cov.:

AF XY:

0.000144

AC XY:

105

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00645

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.00223

AC:

340

AN:

152304

Hom.:

Cov.:

AF XY:

0.00214

AC XY:

159

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00799

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000317

Hom.:

Bravo

AF:

0.00230

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000733

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 24, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

CHAMP1-related disorder

Benign:1

Apr 11, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.077

T;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.63

.;T

MetaRNN

Benign

0.0055

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.90

L;L

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.57

N;.

REVEL

Benign

0.086

Sift

Benign

0.65

T;.

Sift4G

Benign

0.38

T;.

Polyphen

0.0050

B;B

Vest4

0.047

MVP

0.12

MPC

0.16

ClinPred

0.012

GERP RS

5.3

Varity_R

0.040

gMVP

0.092

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over