Genetic Variant CCDC80:p.Arg842Gln (chr3-112605745-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_199511.3(CCDC80):c.2525G>A(p.Arg842Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

CCDC80
NM_199511.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.87

Variant links:

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]

CCDC80 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3946451).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC80	NM_199511.3 link	c.2525G>A	p.Arg842Gln	missense_variant	Exon 8 of 8	ENST00000206423.8	NP_955805.1	Q76M96-1
CCDC80	NM_199512.3 link	c.2525G>A	p.Arg842Gln	missense_variant	Exon 8 of 8		NP_955806.1	Q76M96-1
CCDC80	XM_047447495.1 link	c.2558G>A	p.Arg853Gln	missense_variant	Exon 7 of 7		XP_047303451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCDC80	ENST00000206423.8 link	c.2525G>A	p.Arg842Gln	missense_variant	Exon 8 of 8	1	NM_199511.3	ENSP00000206423.3	Q76M96-1
CCDC80	ENST00000439685.6 link	c.2525G>A	p.Arg842Gln	missense_variant	Exon 8 of 8	1		ENSP00000411814.2	Q76M96-1
CCDC80	ENST00000461431.1 link	c.635G>A	p.Arg212Gln	missense_variant	Exon 6 of 6	3		ENSP00000420123.1	H7C5K4
CCDC80	ENST00000479368.1 link	c.359G>A	p.Arg120Gln	missense_variant	Exon 3 of 3	2		ENSP00000418188.1	C9J8I6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250122

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135272

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000927

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461476

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727020

show subpopulations

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:

0.0000116

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 29, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2525G>A (p.R842Q) 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 2525, causing the arginine (R) at amino acid position 842 to be replaced by a glutamine (Q). 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

Benign

0.15

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.037

T;T;.

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.94

.;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.39

T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.8

L;L;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.29

Sift

Benign

0.12

T;T;T

Sift4G

Pathogenic

0.0

D;D;.

Polyphen

1.0

D;D;.

Vest4

0.60

MutPred

0.23

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);.;

MVP

0.80

MPC

0.74

ClinPred

0.76

GERP RS

5.9

Varity_R

0.22

gMVP

0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over