dbSNP rs200219122: CCDC80:p.Arg776Leu (chr3-112610076-C-A) – 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.2327G>T(p.Arg776Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,612,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CCDC80
NM_199511.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.96

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37579292).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC80	NM_199511.3 link	c.2327G>T	p.Arg776Leu	missense_variant	Exon 6 of 8	ENST00000206423.8	NP_955805.1	Q76M96-1
CCDC80	NM_199512.3 link	c.2327G>T	p.Arg776Leu	missense_variant	Exon 6 of 8		NP_955806.1	Q76M96-1
CCDC80	XM_047447495.1 link	c.2360G>T	p.Arg787Leu	missense_variant	Exon 5 of 7		XP_047303451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCDC80	ENST00000206423.8 link	c.2327G>T	p.Arg776Leu	missense_variant	Exon 6 of 8	1	NM_199511.3	ENSP00000206423.3	Q76M96-1
CCDC80	ENST00000439685.6 link	c.2327G>T	p.Arg776Leu	missense_variant	Exon 6 of 8	1		ENSP00000411814.2	Q76M96-1
CCDC80	ENST00000461431.1 link	c.518G>T	p.Arg173Leu	missense_variant	Exon 5 of 6	3		ENSP00000420123.1	H7C5K4
CCDC80	ENST00000479368.1 link	c.161G>T	p.Arg54Leu	missense_variant	Exon 1 of 3	2		ENSP00000418188.1	C9J8I6

Frequencies

GnomAD3 genomes

AF:

0.00000662

AC:

AN:

151116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461568

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727096

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000662

AC:

AN:

151116

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73790

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Uncertain

0.099

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.052

T;T;.

Eigen

Benign

0.19

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

.;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.38

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.81

L;L;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-2.3

N;N;N

REVEL

Benign

0.22

Sift

Benign

0.16

T;T;T

Sift4G

Pathogenic

0.0

D;D;.

Polyphen

0.27

B;B;.

Vest4

0.81

MutPred

0.51

Loss of MoRF binding (P = 0.0235);Loss of MoRF binding (P = 0.0235);.;

MVP

0.66

MPC

0.74

ClinPred

0.70

GERP RS

5.6

Varity_R

0.088

gMVP

0.72

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over