rs3813133

Variant names:

• chr13-114324718-G-A
• rs3813133
• NM_032436.4:c.876G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_032436.4(CHAMP1):​c.876G>A​(p.Pro292Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.083 in 1,613,386 control chromosomes in the GnomAD database, including 6,368 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.095 (768 hom., cov: 32)
  • Exomes 𝑓: 0.082 (5600 hom.)
• Consequence: CHAMP1 NM_032436.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.597
• Publications: 12 publications found

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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 13-114324718-G-A is Benign according to our data. Variant chr13-114324718-G-A is described in ClinVar as Benign. ClinVar VariationId is 3059016.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.597 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032436.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHAMP1	NM_032436.4	MANE Select	c.876G>A	p.Pro292Pro	synonymous	Exon 3 of 3	NP_115812.1	Q96JM3
	CHAMP1	NM_001164144.3		c.876G>A	p.Pro292Pro	synonymous	Exon 3 of 3	NP_001157616.1	Q96JM3
	CHAMP1	NM_001164145.3		c.876G>A	p.Pro292Pro	synonymous	Exon 3 of 3	NP_001157617.1	Q96JM3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHAMP1	ENST00000361283.4	TSL:1 MANE Select	c.876G>A	p.Pro292Pro	synonymous	Exon 3 of 3	ENSP00000354730.1	Q96JM3
	CHAMP1	ENST00000643483.2		c.876G>A	p.Pro292Pro	synonymous	Exon 3 of 3	ENSP00000496699.1	Q96JM3
	CHAMP1	ENST00000644294.2		c.876G>A	p.Pro292Pro	synonymous	Exon 3 of 3	ENSP00000495985.2	Q96JM3

Frequencies

GnomAD3 genomes AF: 0.0947 AC: 14375 AN: 151850 Hom.: 768 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0974

Gnomad FIN AF: 0.0792

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0704

Gnomad OTH AF: 0.101

GnomAD2 exomes AF: 0.103 AC: 25736 AN: 251048 AF XY: 0.0977

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.204

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.104

Gnomad FIN exome AF: 0.0784

Gnomad NFE exome AF: 0.0738

Gnomad OTH exome AF: 0.0992

GnomAD4 exome AF: 0.0818 AC: 119535 AN: 1461418 Hom.: 5600 Cov.: 32 AF XY: 0.0817 AC XY: 59395 AN XY: 726980

African (AFR) AF: 0.117 AC: 3919 AN: 33462

American (AMR) AF: 0.198 AC: 8845 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 3015 AN: 26106

East Asian (EAS) AF: 0.145 AC: 5765 AN: 39688

South Asian (SAS) AF: 0.0966 AC: 8336 AN: 86252

European-Finnish (FIN) AF: 0.0770 AC: 4112 AN: 53376

Middle Eastern (MID) AF: 0.134 AC: 772 AN: 5766

European-Non Finnish (NFE) AF: 0.0715 AC: 79483 AN: 1111740

Other (OTH) AF: 0.0876 AC: 5288 AN: 60356

GnomAD4 genome AF: 0.0946 AC: 14382 AN: 151968 Hom.: 768 Cov.: 32 AF XY: 0.0968 AC XY: 7189 AN XY: 74288

African (AFR) AF: 0.117 AC: 4856 AN: 41438

American (AMR) AF: 0.142 AC: 2170 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3466

East Asian (EAS) AF: 0.118 AC: 611 AN: 5162

South Asian (SAS) AF: 0.0970 AC: 467 AN: 4812

European-Finnish (FIN) AF: 0.0792 AC: 836 AN: 10558

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0704 AC: 4782 AN: 67944

Other (OTH) AF: 0.100 AC: 211 AN: 2104

Alfa AF: 0.0837 Hom.: 2469

Bravo AF: 0.102

Asia WGS AF: 0.0990 AC: 344 AN: 3478

EpiCase AF: 0.0768

EpiControl AF: 0.0744

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CHAMP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.1
DANN	Benign	0.82
PhyloP100		-0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3813133; hg19: chr13-115090193; COSMIC: COSV63522544; COSMIC: COSV63522544;