3-112610076-C-G

Variant names:

• chr3-112610076-C-G
• NM_199511.3:c.2327G>C

Variant summary

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

The NM_199511.3(CCDC80):​c.2327G>C​(p.Arg776Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,568 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R776Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCDC80 NM_199511.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96

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 rank	MANE	Protein	UniProt
CCDC80	NM_199511.3	c.2327G>C	p.Arg776Pro	missense_variant	Exon 6 of 8	ENST00000206423.8	NP_955805.1
CCDC80	NM_199512.3	c.2327G>C	p.Arg776Pro	missense_variant	Exon 6 of 8		NP_955806.1
CCDC80	XM_047447495.1	c.2360G>C	p.Arg787Pro	missense_variant	Exon 5 of 7		XP_047303451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC80	ENST00000206423.8	c.2327G>C	p.Arg776Pro	missense_variant	Exon 6 of 8	1	NM_199511.3	ENSP00000206423.3
CCDC80	ENST00000439685.6	c.2327G>C	p.Arg776Pro	missense_variant	Exon 6 of 8	1		ENSP00000411814.2
CCDC80	ENST00000461431.1	c.518G>C	p.Arg173Pro	missense_variant	Exon 5 of 6	3		ENSP00000420123.1
CCDC80	ENST00000479368.1	c.161G>C	p.Arg54Pro	missense_variant	Exon 1 of 3	2		ENSP00000418188.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461568 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727096

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;T;.
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	.;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.69	D;D;D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.5	M;M;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.7	D;D;D
REVEL	Uncertain	0.36
Sift	Benign	0.043	D;D;T
Sift4G	Pathogenic	0.0	D;D;.
Polyphen		1.0	D;D;.
Vest4		0.93
MutPred		0.53		Loss of MoRF binding (P = 0.0065);Loss of MoRF binding (P = 0.0065);.;
MVP		0.78
MPC		0.83
ClinPred		0.94	D
GERP RS		5.6
Varity_R		0.50
gMVP		0.83

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: chr3-112328923;