rs3740912

chr11-126021374-C-Gchr11-126021374-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001378964.1(CDON):c.223G>C(p.Val75Leu) 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V75I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CDON NM_001378964.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

Genes affected

CDON (HGNC:17104): (cell adhesion associated, oncogene regulated) This gene encodes a cell surface receptor that is a member of the immunoglobulin superfamily. The encoded protein contains three fibronectin type III domains and five immunoglobulin-like C2-type domains. This protein is a member of a cell-surface receptor complex that mediates cell-cell interactions between muscle precursor cells and positively regulates myogenesis. [provided by RefSeq, Aug 2011]

ACMG classification

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=0.101545215).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDON	NM_001378964.1	c.223G>C	p.Val75Leu	missense_variant	3/20	ENST00000531738.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDON	ENST00000531738.6	c.223G>C	p.Val75Leu	missense_variant	3/20	1	NM_001378964.1	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	11
Dann	Benign	0.66
DEOGEN2	Benign	0.25	T;.;.;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.25	T;T;T;T;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.10	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L;L;.;.;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.90	N;N;N;N;N
REVEL	Benign	0.081
Sift	Benign	0.42	T;T;T;T;T
Sift4G	Benign	0.45	T;T;.;.;.
Polyphen		0.0010	B;B;B;.;.
Vest4		0.14
MutPred		0.58		Gain of catalytic residue at V75 (P = 0.074);Gain of catalytic residue at V75 (P = 0.074);Gain of catalytic residue at V75 (P = 0.074);Gain of catalytic residue at V75 (P = 0.074);Gain of catalytic residue at V75 (P = 0.074);
MVP		0.27
MPC		0.098
ClinPred		0.053	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.44

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

Other links and lift over

dbSNP: rs3740912; hg19: chr11-125891269;