3-112605745-C-T

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

5
4
10

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]

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
CCDC80NM_199511.3 linkc.2525G>A p.Arg842Gln missense_variant Exon 8 of 8 ENST00000206423.8 NP_955805.1 Q76M96-1
CCDC80NM_199512.3 linkc.2525G>A p.Arg842Gln missense_variant Exon 8 of 8 NP_955806.1 Q76M96-1
CCDC80XM_047447495.1 linkc.2558G>A p.Arg853Gln missense_variant Exon 7 of 7 XP_047303451.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC80ENST00000206423.8 linkc.2525G>A p.Arg842Gln missense_variant Exon 8 of 8 1 NM_199511.3 ENSP00000206423.3 Q76M96-1
CCDC80ENST00000439685.6 linkc.2525G>A p.Arg842Gln missense_variant Exon 8 of 8 1 ENSP00000411814.2 Q76M96-1
CCDC80ENST00000461431.1 linkc.635G>A p.Arg212Gln missense_variant Exon 6 of 6 3 ENSP00000420123.1 H7C5K4
CCDC80ENST00000479368.1 linkc.359G>A p.Arg120Gln missense_variant Exon 3 of 3 2 ENSP00000418188.1 C9J8I6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000160
AC:
4
AN:
250122
Hom.:
0
AF XY:
0.0000148
AC XY:
2
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:
9
AN:
1461476
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
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.:
33
ExAC
AF:
0.00000824
AC:
1

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
D
BayesDel_noAF
Uncertain
0.040
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.037
T;T;.
Eigen
Pathogenic
0.81
Eigen_PC
Pathogenic
0.83
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.94
.;D;D
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.39
T;T;T
MetaSVM
Benign
-0.69
T
MutationAssessor
Benign
1.8
L;L;.
PrimateAI
Uncertain
0.52
T
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
D
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.

Other links and lift over

dbSNP: rs757129900; hg19: chr3-112324592; API