rs34564491

Variant names:

• chr16-50749785-C-A
• NM_001378743.1:c.87C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-50749785-C-A
• chr16-50749785-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001378743.1(CYLD):​c.87C>A​(p.Ser29Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S29S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CYLD NM_001378743.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37500226).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYLD	NM_001378743.1	c.87C>A	p.Ser29Arg	missense_variant	Exon 3 of 19	ENST00000427738.8	NP_001365672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYLD	ENST00000427738.8	c.87C>A	p.Ser29Arg	missense_variant	Exon 3 of 19	5	NM_001378743.1	ENSP00000392025.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.030	T;.;T;.;T;.;.;.;T;.
Eigen	Benign	-0.023
Eigen_PC	Benign	-0.010
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.89	D;D;.;.;D;D;D;.;D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.38	T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.17	D
MutationAssessor	Benign	0.81	.;L;L;L;.;.;.;L;L;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.2	N;N;N;N;.;N;D;N;N;N
REVEL	Uncertain	0.51
Sift	Benign	0.24	T;D;D;D;.;T;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D
Polyphen		0.98, 0.97	.;D;D;D;.;.;.;D;D;.
Vest4		0.48, 0.51, 0.48, 0.49, 0.49, 0.51, 0.50
MutPred		0.25		Gain of MoRF binding (P = 0.0167);Gain of MoRF binding (P = 0.0167);Gain of MoRF binding (P = 0.0167);Gain of MoRF binding (P = 0.0167);Gain of MoRF binding (P = 0.0167);Gain of MoRF binding (P = 0.0167);Gain of MoRF binding (P = 0.0167);Gain of MoRF binding (P = 0.0167);Gain of MoRF binding (P = 0.0167);Gain of MoRF binding (P = 0.0167);
MVP		0.92
MPC		1.0
ClinPred		0.84	D
GERP RS		2.0
Varity_R		0.39
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-50783696;