chr3-112616846-C-A

Variant names:

• chr3-112616846-C-A
• rs1935762251
• NM_199511.3:c.2185G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_199511.3(CCDC80):​c.2185G>T​(p.Val729Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V729I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC80 NM_199511.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.42
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199511.3. 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
	CCDC80	NM_199511.3	MANE Select	c.2185G>T	p.Val729Leu	missense	Exon 5 of 8	NP_955805.1	Q76M96-1
	CCDC80	NM_199512.3		c.2185G>T	p.Val729Leu	missense	Exon 5 of 8	NP_955806.1	Q76M96-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC80	ENST00000206423.8	TSL:1 MANE Select	c.2185G>T	p.Val729Leu	missense	Exon 5 of 8	ENSP00000206423.3	Q76M96-1
	CCDC80	ENST00000439685.6	TSL:1	c.2185G>T	p.Val729Leu	missense	Exon 5 of 8	ENSP00000411814.2	Q76M96-1
	CCDC80	ENST00000880155.1		c.2185G>T	p.Val729Leu	missense	Exon 5 of 8	ENSP00000550214.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		7.4
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.23
Sift	Benign	0.064	T
Sift4G	Uncertain	0.0070	D
Polyphen		0.99	D
Vest4		0.86
MutPred		0.44		Loss of methylation at K724 (P = 0.0715)
MVP		0.68
MPC		0.68
ClinPred		0.90	D
GERP RS		5.7
Varity_R		0.24
gMVP		0.52
Mutation Taster		=38/62	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1935762251; hg19: chr3-112335693;