rs764097337

Variant names:

• chr16-50749757-T-A
• rs764097337
• NM_001378743.1:c.59T>A

Your query was ambiguous. Multiple possible variants found:

• chr16-50749757-T-A
• chr16-50749757-T-G

Variant summary

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

The NM_001378743.1(CYLD):​c.59T>A​(p.Ile20Asn) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CYLD NM_001378743.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3103931).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYLD	NM_001378743.1	c.59T>A	p.Ile20Asn	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.59T>A	p.Ile20Asn	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	Benign	0.31
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	7.6
DANN	Benign	0.82
DEOGEN2	Benign	0.037	T;.;T;.;T;.;.;.;T;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.62
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.79	T;T;.;.;T;T;T;.;T;T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.31	T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	0.81	.;L;L;L;.;.;.;L;L;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.6	N;N;N;N;.;N;D;N;N;N
REVEL	Uncertain	0.31
Sift	Benign	0.18	T;D;D;D;.;T;D;D;D;D
Sift4G	Uncertain	0.047	D;D;D;D;D;D;D;D;D;D
Polyphen		0.37, 0.087	.;B;B;B;.;.;.;B;B;.
Vest4		0.57, 0.55, 0.81, 0.56, 0.57, 0.56, 0.53
MutPred		0.40		Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);
MVP		0.80
MPC		0.77
ClinPred		0.24	T
GERP RS		-0.70
Varity_R		0.15
gMVP		0.41

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: rs764097337; hg19: chr16-50783668;