3-112616720-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 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

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	UniProt
CCDC80	NM_199511.3	c.2311T>G	p.Phe771Val	missense_variant	5/8	ENST00000206423.8
CCDC80	NM_199512.3	c.2311T>G	p.Phe771Val	missense_variant	5/8
CCDC80	XM_047447495.1	c.2344T>G	p.Phe782Val	missense_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC80	ENST00000206423.8	c.2311T>G	p.Phe771Val	missense_variant	5/8	1	NM_199511.3	P1
CCDC80	ENST00000439685.6	c.2311T>G	p.Phe771Val	missense_variant	5/8	1		P1
CCDC80	ENST00000461431.1	c.505T>G	p.Phe169Val	missense_variant	4/6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Jul 09, 2021

The c.2311T>G (p.F771V) alteration is located in exon 5 (coding exon 4) of the CCDC80 gene. This alteration results from a T to G substitution at nucleotide position 2311, causing the phenylalanine (F) at amino acid position 771 to be replaced by a valine (V). 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	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;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	1.0	D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.6	D;D
REVEL	Uncertain	0.43
Sift	Uncertain	0.029	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.99	D;D
Vest4		0.89
MutPred		0.29		Gain of helix (P = 0.0164);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-112335567;