chr16-50749722-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_001378743.1(CYLD):c.24A>C(p.Gln8His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
CYLD
NM_001378743.1 missense
NM_001378743.1 missense
Scores
6
7
4
Clinical Significance
Conservation
PhyloP100: 7.14
Genes affected
CYLD (HGNC:2584): (CYLD lysine 63 deubiquitinase) This gene is encodes a cytoplasmic protein with three cytoskeletal-associated protein-glycine-conserved (CAP-GLY) domains that functions as a deubiquitinating enzyme. Mutations in this gene have been associated with cylindromatosis, multiple familial trichoepithelioma, and Brooke-Spiegler syndrome. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, CYLD
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYLD | NM_001378743.1 | c.24A>C | p.Gln8His | missense_variant | 3/19 | ENST00000427738.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYLD | ENST00000427738.8 | c.24A>C | p.Gln8His | missense_variant | 3/19 | 5 | NM_001378743.1 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2023 | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 8 of the CYLD protein (p.Gln8His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CYLD-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CYLD protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;T;.;T;.;.;.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.;.;D;D;D;.;D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D;D;D;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;.;N;D;N;N;N
Sift
Pathogenic
D;D;D;D;.;D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D;D;D;D;D;D
Polyphen
1.0, 1.0
.;D;D;D;.;.;.;D;D;.
Vest4
0.60, 0.58, 0.63, 0.61, 0.55
MutPred
Gain of glycosylation at S3 (P = 0.073);Gain of glycosylation at S3 (P = 0.073);Gain of glycosylation at S3 (P = 0.073);Gain of glycosylation at S3 (P = 0.073);Gain of glycosylation at S3 (P = 0.073);Gain of glycosylation at S3 (P = 0.073);Gain of glycosylation at S3 (P = 0.073);Gain of glycosylation at S3 (P = 0.073);Gain of glycosylation at S3 (P = 0.073);Gain of glycosylation at S3 (P = 0.073);
MVP
MPC
1.2
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.