6-53005156-C-G

Position:

• chr6-53005156-C-G

Variant summary

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

The NM_014920.5(CILK1):​c.1892G>C​(p.Arg631Pro) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R631Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CILK1 NM_014920.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.47

Genes affected

CILK1 (HGNC:21219): (ciliogenesis associated kinase 1) Eukaryotic protein kinases are enzymes that belong to a very extensive family of proteins which share a conserved catalytic core common with both serine/threonine and tyrosine protein kinases. This gene encodes an intestinal serine/threonine kinase harboring a dual phosphorylation site found in mitogen-activating protein (MAP) kinases. The protein localizes to the intestinal crypt region and is thought to be important in intestinal epithelial cell proliferation and differentiation. Alternative splicing has been observed at this locus and two variants, encoding the same isoform, have been identified. [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=0.19606736).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CILK1	NM_014920.5	c.1892G>C	p.Arg631Pro	missense_variant	14/14	ENST00000676107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CILK1	ENST00000676107.1	c.1892G>C	p.Arg631Pro	missense_variant	14/14		NM_014920.5	P1
CILK1	ENST00000350082.10	c.1913G>C	p.Arg638Pro	missense_variant	14/14	1
CILK1	ENST00000356971.3	c.1892G>C	p.Arg631Pro	missense_variant	15/15	2		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 22, 2022

The c.1892G>C (p.R631P) alteration is located in exon 15 (coding exon 13) of the ICK gene. This alteration results from a G to C substitution at nucleotide position 1892, causing the arginine (R) at amino acid position 631 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T;T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.59	.;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.1	L;L
MutationTaster	Benign	0.96	D;D
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.4	N;N
REVEL	Uncertain	0.33
Sift	Uncertain	0.0050	D;D
Sift4G	Benign	0.14	T;T
Polyphen		0.96	D;D
Vest4		0.17
MutPred		0.36		Gain of glycosylation at R631 (P = 0.0251);Gain of glycosylation at R631 (P = 0.0251);
MVP		0.79
MPC		0.70
ClinPred		0.82	D
GERP RS		6.0
Varity_R		0.51
gMVP		0.30

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: chr6-52869954;