3-112616794-C-G

Variant summary

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

The NM_199511.3(CCDC80):ā€‹c.2237G>Cā€‹(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 (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.000027 ( 0 hom. )

Consequence

CCDC80
NM_199511.3 missense

Scores

8
7
4

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]

Genome browser will be placed here

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
CCDC80NM_199511.3 linkc.2237G>C p.Arg746Pro missense_variant 5/8 ENST00000206423.8 NP_955805.1 Q76M96-1
CCDC80NM_199512.3 linkc.2237G>C p.Arg746Pro missense_variant 5/8 NP_955806.1 Q76M96-1
CCDC80XM_047447495.1 linkc.2270G>C p.Arg757Pro missense_variant 4/7 XP_047303451.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC80ENST00000206423.8 linkc.2237G>C p.Arg746Pro missense_variant 5/81 NM_199511.3 ENSP00000206423.3 Q76M96-1
CCDC80ENST00000439685.6 linkc.2237G>C p.Arg746Pro missense_variant 5/81 ENSP00000411814.2 Q76M96-1
CCDC80ENST00000461431.1 linkc.428G>C p.Arg143Pro missense_variant 4/63 ENSP00000420123.1 H7C5K4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.0000267
AC:
39
AN:
1461830
Hom.:
0
Cov.:
31
AF XY:
0.0000275
AC XY:
20
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.:
32
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 submitterclinical testingAmbry GeneticsAug 21, 2024The 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
D
BayesDel_noAF
Pathogenic
0.22
CADD
Pathogenic
32
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
T;T
Eigen
Pathogenic
0.89
Eigen_PC
Pathogenic
0.88
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
.;D
M_CAP
Benign
0.047
D
MetaRNN
Pathogenic
0.86
D;D
MetaSVM
Uncertain
-0.16
T
MutationAssessor
Uncertain
2.5
M;M
PrimateAI
Pathogenic
0.80
T
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
D
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.

Other links and lift over

dbSNP: rs756967937; hg19: chr3-112335641; API