chr3-112616720-A-C

Variant names:

• chr3-112616720-A-C
• NM_199511.3:c.2311T>G

Variant summary

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

The NM_199511.3(CCDC80):​c.2311T>G​(p.Phe771Val) 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: 8.76
• 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.2311T>G	p.Phe771Val	missense	Exon 5 of 8	NP_955805.1	Q76M96-1
	CCDC80	NM_199512.3		c.2311T>G	p.Phe771Val	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.2311T>G	p.Phe771Val	missense	Exon 5 of 8	ENSP00000206423.3	Q76M96-1
	CCDC80	ENST00000439685.6	TSL:1	c.2311T>G	p.Phe771Val	missense	Exon 5 of 8	ENSP00000411814.2	Q76M96-1
	CCDC80	ENST00000880155.1		c.2311T>G	p.Phe771Val	missense	Exon 5 of 8	ENSP00000550214.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		8.8
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.029	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.89
MutPred		0.29		Gain of helix (P = 0.0164)
MVP		0.74
MPC		0.79
ClinPred		0.97	D
GERP RS		5.8
Varity_R		0.46
gMVP		0.56
Mutation Taster		=32/68	disease causing

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

hg19: chr3-112335567;