13-114323927-G-A

Position:

• chr13-114323927-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_032436.4(CHAMP1):​c.85G>A​(p.Val29Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: CHAMP1 NM_032436.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.77

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12956819).
• BS2: High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHAMP1	NM_032436.4	c.85G>A	p.Val29Ile	missense_variant	3/3	ENST00000361283.4	NP_115812.1
CHAMP1	NM_001164144.3	c.85G>A	p.Val29Ile	missense_variant	3/3		NP_001157616.1
CHAMP1	NM_001164145.3	c.85G>A	p.Val29Ile	missense_variant	3/3		NP_001157617.1
CHAMP1	XM_047430277.1	c.85G>A	p.Val29Ile	missense_variant	3/3		XP_047286233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHAMP1	ENST00000361283.4	c.85G>A	p.Val29Ile	missense_variant	3/3	1	NM_032436.4	ENSP00000354730.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727242

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000135

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2024

CHAMP1: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T;T;.;.;T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.75	.;T;T;T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.0	L;.;.;.;L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.090	N;.;.;.;.
REVEL	Benign	0.072
Sift	Benign	0.41	T;.;.;.;.
Sift4G	Benign	0.63	T;T;.;.;.
Polyphen		0.72	P;.;.;.;P
Vest4		0.042
MutPred		0.24		Gain of catalytic residue at H32 (P = 0.0013);Gain of catalytic residue at H32 (P = 0.0013);Gain of catalytic residue at H32 (P = 0.0013);Gain of catalytic residue at H32 (P = 0.0013);Gain of catalytic residue at H32 (P = 0.0013);
MVP		0.36
MPC		0.18
ClinPred		0.36	T
GERP RS		5.8
Varity_R		0.024
gMVP		0.21

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: chr13-115089402;