Variant 13-114324333-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032436.4(CHAMP1):c.491C>T(p.Ser164Phe) variant causes a missense 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S164P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CHAMP1
NM_032436.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.27

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23234868).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CHAMP1	NM_032436.4 linkuse as main transcript	c.491C>T	p.Ser164Phe	missense_variant	3/3	ENST00000361283.4
CHAMP1	NM_001164144.3 linkuse as main transcript	c.491C>T	p.Ser164Phe	missense_variant	3/3
CHAMP1	NM_001164145.3 linkuse as main transcript	c.491C>T	p.Ser164Phe	missense_variant	3/3
CHAMP1	XM_047430277.1 linkuse as main transcript	c.491C>T	p.Ser164Phe	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHAMP1	ENST00000361283.4 linkuse as main transcript	c.491C>T	p.Ser164Phe	missense_variant	3/3	1	NM_032436.4	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727244

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Intellectual disability, autosomal dominant 40

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

New York Genome Center

Mar 02, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

D;.;D

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.78

M_CAP

Benign

0.0073

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.6

L;.;L

MutationTaster

Benign

0.94

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.0

D;.;.

REVEL

Benign

0.13

Sift

Uncertain

0.0010

D;.;.

Sift4G

Uncertain

0.0070

D;.;.

Polyphen

0.94

P;.;P

Vest4

0.29

MutPred

0.32

Gain of catalytic residue at E166 (P = 0.0012);Gain of catalytic residue at E166 (P = 0.0012);Gain of catalytic residue at E166 (P = 0.0012);

MVP

0.17

MPC

0.41

ClinPred

0.93

GERP RS

5.8

Varity_R

0.16

gMVP

0.28

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over