rs587778224

Positions:

• chr16-50750042-A-G
• chr16-50750042-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001378743.1(CYLD):​c.344A>G​(p.Asn115Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CYLD NM_001378743.1 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 4.80

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19310841).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYLD	NM_001378743.1	c.344A>G	p.Asn115Ser	missense_variant	3/19	ENST00000427738.8	NP_001365672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYLD	ENST00000427738.8	c.344A>G	p.Asn115Ser	missense_variant	3/19	5	NM_001378743.1	ENSP00000392025.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.094	T;.;T;.;T;.;.;T;.
Eigen	Benign	-0.056
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D;D;.;.;D;D;.;D;D
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.19	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.55	.;N;N;N;.;.;N;N;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.2	N;N;N;N;.;N;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.14	T;T;T;T;.;T;T;T;D
Sift4G	Benign	0.16	T;T;T;T;T;T;T;T;T
Polyphen		0.011, 0.0070	.;B;B;B;.;.;B;B;.
Vest4		0.11, 0.10, 0.13, 0.13, 0.12, 0.10
MutPred		0.25		Gain of sheet (P = 0.0061);Gain of sheet (P = 0.0061);Gain of sheet (P = 0.0061);Gain of sheet (P = 0.0061);Gain of sheet (P = 0.0061);Gain of sheet (P = 0.0061);Gain of sheet (P = 0.0061);Gain of sheet (P = 0.0061);Gain of sheet (P = 0.0061);
MVP		0.71
MPC		0.32
ClinPred		0.65	D
GERP RS		6.2
Varity_R		0.050
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs587778224; hg19: chr16-50783953;