Variant chr3-112607200-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_199511.3(CCDC80):c.2482G>A(p.Val828Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,472 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: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CCDC80
NM_199511.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.45

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=0.34233645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CCDC80	NM_199511.3 linkuse as main transcript	c.2482G>A	p.Val828Met	missense_variant	7/8	ENST00000206423.8
CCDC80	NM_199512.3 linkuse as main transcript	c.2482G>A	p.Val828Met	missense_variant	7/8
CCDC80	XM_047447495.1 linkuse as main transcript	c.2515G>A	p.Val839Met	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC80	ENST00000206423.8 linkuse as main transcript	c.2482G>A	p.Val828Met	missense_variant	7/8	1	NM_199511.3	P1	Q76M96-1
CCDC80	ENST00000439685.6 linkuse as main transcript	c.2482G>A	p.Val828Met	missense_variant	7/8	1		P1	Q76M96-1
CCDC80	ENST00000479368.1 linkuse as main transcript	c.316G>A	p.Val106Met	missense_variant	2/3	2
CCDC80	ENST00000461431.1 linkuse as main transcript	c.618-1437G>A		intron_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461472

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 15, 2022

The c.2482G>A (p.V828M) alteration is located in exon 7 (coding exon 6) of the CCDC80 gene. This alteration results from a G to A substitution at nucleotide position 2482, causing the valine (V) at amino acid position 828 to be replaced by a methionine (M). 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

0.13

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

T;T;.

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

.;D;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.34

T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.1

M;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.0

N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0030

D;D;D

Sift4G

Pathogenic

0.0

D;D;.

Polyphen

0.79

P;P;.

Vest4

0.68

MutPred

0.29

Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);.;

MVP

0.51

MPC

0.66

ClinPred

0.86

GERP RS

4.9

Varity_R

0.27

gMVP

0.32

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over