Variant 3-112616794-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_199511.3(CCDC80):c.2237G>C(p.Arg746Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

CCDC80
NM_199511.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.42

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.858

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC80	NM_199511.3 link	c.2237G>C	p.Arg746Pro	missense_variant	5/8	ENST00000206423.8	NP_955805.1	Q76M96-1
CCDC80	NM_199512.3 link	c.2237G>C	p.Arg746Pro	missense_variant	5/8		NP_955806.1	Q76M96-1
CCDC80	XM_047447495.1 link	c.2270G>C	p.Arg757Pro	missense_variant	4/7		XP_047303451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC80	ENST00000206423.8 link	c.2237G>C	p.Arg746Pro	missense_variant	5/8	1	NM_199511.3	ENSP00000206423.3	Q76M96-1
CCDC80	ENST00000439685.6 link	c.2237G>C	p.Arg746Pro	missense_variant	5/8	1		ENSP00000411814.2	Q76M96-1
CCDC80	ENST00000461431.1 link	c.428G>C	p.Arg143Pro	missense_variant	4/6	3		ENSP00000420123.1	H7C5K4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000267

AC:

AN:

1461830

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727214

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000351

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 21, 2024

The c.2237G>C (p.R746P) alteration is located in exon 5 (coding exon 4) of the CCDC80 gene. This alteration results from a G to C substitution at nucleotide position 2237, causing the arginine (R) at amino acid position 746 to be replaced by a proline (P). 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

0.99

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

.;D

M_CAP

Benign

0.047

MetaRNN

Pathogenic

0.86

D;D

MetaSVM

Uncertain

-0.16

MutationAssessor

Uncertain

2.5

M;M

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-3.7

D;D

REVEL

Uncertain

0.56

Sift

Benign

0.10

T;T

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;D

Vest4

0.97

MVP

0.94

MPC

0.83

ClinPred

0.99

GERP RS

5.8

Varity_R

0.87

gMVP

0.97

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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