rs866583645

Variant names:

• chr19-15053615-G-A
• rs866583645
• NM_012114.3:c.161G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-15053615-G-A
• chr19-15053615-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012114.3(CASP14):​c.161G>A​(p.Arg54Lys) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R54T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CASP14 NM_012114.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500
• Publications: 1 publications found

Genes affected

CASP14 (HGNC:1502): (caspase 14) This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This caspase has been shown to be processed and activated by caspase 8 and caspase 10 in vitro, and by anti-Fas agonist antibody or TNF-related apoptosis inducing ligand in vivo. The expression and processing of this caspase may be involved in keratinocyte terminal differentiation, which is important for the formation of the skin barrier. [provided by RefSeq, Jul 2008]

ENSG00000302149 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06866276).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012114.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP14	NM_012114.3	MANE Select	c.161G>A	p.Arg54Lys	missense	Exon 3 of 7	NP_036246.1	P31944

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP14	ENST00000427043.4	TSL:1 MANE Select	c.161G>A	p.Arg54Lys	missense	Exon 3 of 7	ENSP00000393417.2	P31944
	ENSG00000302149	ENST00000784685.1		n.233-920C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.4
DANN	Benign	0.92
DEOGEN2	Benign	0.055	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.91	L
PhyloP100		0.050
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.015
Sift	Benign	0.94	T
Sift4G	Benign	1.0	T
Polyphen		0.0060	B
Vest4		0.29
MutPred		0.33		Gain of ubiquitination at R54 (P = 0.0054)
MVP		0.095
MPC		0.031
ClinPred		0.029	T
GERP RS		1.6
Varity_R		0.057
gMVP		0.45
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs866583645; hg19: chr19-15164426; COSMIC: COSV107287520; COSMIC: COSV107287520;