3-112605527-C-T

Variant summary

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

The NM_199511.3(CCDC80):c.2743G>A(p.Glu915Lys) 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: 33)
• Consequence: CCDC80 NM_199511.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.87

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.2743G>A	p.Glu915Lys	missense_variant	8/8	ENST00000206423.8
CCDC80	NM_199512.3	c.2743G>A	p.Glu915Lys	missense_variant	8/8
CCDC80	XM_047447495.1	c.2776G>A	p.Glu926Lys	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC80	ENST00000206423.8	c.2743G>A	p.Glu915Lys	missense_variant	8/8	1	NM_199511.3	P1
CCDC80	ENST00000439685.6	c.2743G>A	p.Glu915Lys	missense_variant	8/8	1		P1
CCDC80	ENST00000479368.1	c.577G>A	p.Glu193Lys	missense_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Jun 27, 2022

The c.2743G>A (p.E915K) alteration is located in exon 8 (coding exon 7) of the CCDC80 gene. This alteration results from a G to A substitution at nucleotide position 2743, causing the glutamic acid (E) at amino acid position 915 to be replaced by a lysine (K). 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	0.77
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
Cadd	Pathogenic	33
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.036	T;T;.
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.0	L;L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.0040	D;D;.
Polyphen		1.0	D;D;.
Vest4		0.38
MutPred		0.49		Gain of solvent accessibility (P = 4e-04);Gain of solvent accessibility (P = 4e-04);.;
MVP		0.81
MPC		0.64
ClinPred		0.90	D
GERP RS		5.8
Varity_R		0.36
gMVP		0.55

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: chr3-112324374;