3-112616846-C-T

Position:

• chr3-112616846-C-T

Variant summary

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

The NM_199511.3(CCDC80):​c.2185G>A​(p.Val729Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC80 NM_199511.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.42

Genes affected

CCDC80 (HGNC:30649): (coiled-coil domain containing 80) Predicted to enable glycosaminoglycan binding activity. Predicted to act upstream of or within extracellular matrix organization; positive regulation of cell-substrate adhesion; and response to bacterium. Predicted to be located in extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC80	NM_199511.3	c.2185G>A	p.Val729Ile	missense_variant	5/8	ENST00000206423.8	NP_955805.1
CCDC80	NM_199512.3	c.2185G>A	p.Val729Ile	missense_variant	5/8		NP_955806.1
CCDC80	XM_047447495.1	c.2218G>A	p.Val740Ile	missense_variant	4/7		XP_047303451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC80	ENST00000206423.8	c.2185G>A	p.Val729Ile	missense_variant	5/8	1	NM_199511.3	ENSP00000206423.3
CCDC80	ENST00000439685.6	c.2185G>A	p.Val729Ile	missense_variant	5/8	1		ENSP00000411814.2
CCDC80	ENST00000461431.1	c.376G>A	p.Val126Ile	missense_variant	4/6	3		ENSP00000420123.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 05, 2024

The c.2185G>A (p.V729I) alteration is located in exon 5 (coding exon 4) of the CCDC80 gene. This alteration results from a G to A substitution at nucleotide position 2185, causing the valine (V) at amino acid position 729 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T;T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.95	.;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.50	N;N
REVEL	Benign	0.18
Sift	Benign	0.033	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.99	D;D
Vest4		0.56
MutPred		0.43		Loss of catalytic residue at V729 (P = 0.0645);Loss of catalytic residue at V729 (P = 0.0645);
MVP		0.67
MPC		0.62
ClinPred		0.81	D
GERP RS		5.7
Varity_R		0.14
gMVP		0.35

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: rs1935762251; hg19: chr3-112335693;