13-114323909-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032436.4(CHAMP1):c.67G>A(p.Gly23Ser) variant causes a missense change. 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHAMP1 NM_032436.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.75

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41377023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHAMP1	NM_032436.4	c.67G>A	p.Gly23Ser	missense_variant	3/3	ENST00000361283.4
CHAMP1	NM_001164144.3	c.67G>A	p.Gly23Ser	missense_variant	3/3
CHAMP1	NM_001164145.3	c.67G>A	p.Gly23Ser	missense_variant	3/3
CHAMP1	XM_047430277.1	c.67G>A	p.Gly23Ser	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHAMP1	ENST00000361283.4	c.67G>A	p.Gly23Ser	missense_variant	3/3	1	NM_032436.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

See cases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Medicine, Universita Cattolica del Sacro Cuore

Dec 21, 2022

The variant is de novo and it is not reported in the gnomAD database. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
Cadd	Pathogenic	26
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.21	T;T;.;.;T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.41	T;T;T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.9	L;.;.;.;L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-2.1	N;.;.;.;.
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D;.;.;.;.
Sift4G	Pathogenic	0.0	D;D;.;.;.
Polyphen		1.0	D;.;.;.;D
Vest4		0.71
MutPred		0.42		Gain of catalytic residue at R22 (P = 0);Gain of catalytic residue at R22 (P = 0);Gain of catalytic residue at R22 (P = 0);Gain of catalytic residue at R22 (P = 0);Gain of catalytic residue at R22 (P = 0);
MVP		0.40
MPC		0.51
ClinPred		0.87	D
GERP RS		5.8
Varity_R		0.16
gMVP		0.55

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.

Other links and lift over

hg19: chr13-115089384;