3-112638045-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_199511.3(CCDC80):c.1861G>A(p.Gly621Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000686 in 1,603,638 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: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
CCDC80
NM_199511.3 missense
NM_199511.3 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 5.01
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]
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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=0.34009036).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC80 | NM_199511.3 | c.1861G>A | p.Gly621Ser | missense_variant | 2/8 | ENST00000206423.8 | |
CCDC80 | NM_199512.3 | c.1861G>A | p.Gly621Ser | missense_variant | 2/8 | ||
CCDC80 | XM_047447495.1 | c.1894G>A | p.Gly632Ser | missense_variant | 1/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC80 | ENST00000206423.8 | c.1861G>A | p.Gly621Ser | missense_variant | 2/8 | 1 | NM_199511.3 | P1 | |
CCDC80 | ENST00000439685.6 | c.1861G>A | p.Gly621Ser | missense_variant | 2/8 | 1 | P1 | ||
CCDC80 | ENST00000461431.1 | c.55G>A | p.Gly19Ser | missense_variant | 1/6 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152164Hom.: 0 Cov.: 31
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000837 AC: 2AN: 238818Hom.: 0 AF XY: 0.0000155 AC XY: 2AN XY: 129116
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GnomAD4 exome AF: 0.00000620 AC: 9AN: 1451474Hom.: 0 Cov.: 33 AF XY: 0.00000554 AC XY: 4AN XY: 721746
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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 | May 30, 2023 | The c.1861G>A (p.G621S) alteration is located in exon 2 (coding exon 1) of the CCDC80 gene. This alteration results from a G to A substitution at nucleotide position 1861, causing the glycine (G) at amino acid position 621 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
D;D
Sift4G
Benign
T;T
Polyphen
P;P
Vest4
MutPred
Gain of phosphorylation at G621 (P = 0.0471);Gain of phosphorylation at G621 (P = 0.0471);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at