11-86387610-T-G
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001156474.2(CCDC81):āc.236T>Gā(p.Phe79Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,612,194 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: š 0.000085 ( 0 hom., cov: 33)
Exomes š: 0.0000068 ( 0 hom. )
Consequence
CCDC81
NM_001156474.2 missense
NM_001156474.2 missense
Scores
9
7
3
Clinical Significance
Conservation
PhyloP100: 5.34
Genes affected
CCDC81 (HGNC:26281): (coiled-coil domain containing 81) Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.982
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CCDC81 | NM_001156474.2 | c.236T>G | p.Phe79Cys | missense_variant | 3/15 | ENST00000445632.7 | NP_001149946.1 | |
CCDC81 | NM_021827.5 | c.236T>G | p.Phe79Cys | missense_variant | 3/14 | NP_068599.3 | ||
LOC105369421 | XR_007062825.1 | n.210+157A>C | intron_variant | |||||
LOC105369421 | XR_007062826.1 | n.188+157A>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CCDC81 | ENST00000445632.7 | c.236T>G | p.Phe79Cys | missense_variant | 3/15 | 1 | NM_001156474.2 | ENSP00000415528.2 | ||
CCDC81 | ENST00000354755.5 | c.236T>G | p.Phe79Cys | missense_variant | 3/14 | 2 | ENSP00000346800.1 | |||
CCDC81 | ENST00000531271.5 | c.141+1498T>G | intron_variant | 3 | ENSP00000434959.1 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152184Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251184Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135756
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GnomAD4 exome AF: 0.00000685 AC: 10AN: 1460010Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 2AN XY: 726432
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GnomAD4 genome AF: 0.0000854 AC: 13AN: 152184Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74352
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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 | Apr 07, 2023 | The c.236T>G (p.F79C) alteration is located in exon 3 (coding exon 3) of the CCDC81 gene. This alteration results from a T to G substitution at nucleotide position 236, causing the phenylalanine (F) at amino acid position 79 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Loss of catalytic residue at F79 (P = 0.0846);Loss of catalytic residue at F79 (P = 0.0846);
MVP
MPC
0.74
ClinPred
D
GERP RS
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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