11-86387610-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001156474.2(CCDC81):ā€‹c.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

Scores

9
7
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.34
Variant links:
Genes affected
CCDC81 (HGNC:26281): (coiled-coil domain containing 81) Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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
CCDC81NM_001156474.2 linkuse as main transcriptc.236T>G p.Phe79Cys missense_variant 3/15 ENST00000445632.7 NP_001149946.1 Q6ZN84-1
CCDC81NM_021827.5 linkuse as main transcriptc.236T>G p.Phe79Cys missense_variant 3/14 NP_068599.3 Q6ZN84-2
LOC105369421XR_007062825.1 linkuse as main transcriptn.210+157A>C intron_variant
LOC105369421XR_007062826.1 linkuse as main transcriptn.188+157A>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC81ENST00000445632.7 linkuse as main transcriptc.236T>G p.Phe79Cys missense_variant 3/151 NM_001156474.2 ENSP00000415528.2 Q6ZN84-1
CCDC81ENST00000354755.5 linkuse as main transcriptc.236T>G p.Phe79Cys missense_variant 3/142 ENSP00000346800.1 Q6ZN84-2
CCDC81ENST00000531271.5 linkuse as main transcriptc.141+1498T>G intron_variant 3 ENSP00000434959.1 E9PMI9

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152184
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000785
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251184
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135756
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.00000685
AC:
10
AN:
1460010
Hom.:
0
Cov.:
29
AF XY:
0.00000275
AC XY:
2
AN XY:
726432
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000157
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:
0.00
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152184
Hom.:
0
Cov.:
33
AF XY:
0.0000807
AC XY:
6
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000785
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000212

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 GeneticsApr 07, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.91
BayesDel_addAF
Pathogenic
0.34
D
BayesDel_noAF
Pathogenic
0.33
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.30
.;T
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.84
T;T
M_CAP
Uncertain
0.22
D
MetaRNN
Pathogenic
0.98
D;D
MetaSVM
Uncertain
0.27
D
MutationAssessor
Pathogenic
2.9
M;M
MutationTaster
Benign
0.64
D;D;D
PrimateAI
Uncertain
0.66
T
PROVEAN
Pathogenic
-5.8
D;D
REVEL
Pathogenic
0.71
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.94
MutPred
0.83
Loss of catalytic residue at F79 (P = 0.0846);Loss of catalytic residue at F79 (P = 0.0846);
MVP
0.83
MPC
0.74
ClinPred
0.99
D
GERP RS
5.3
Varity_R
0.80
gMVP
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs866033325; hg19: chr11-86098652; API