rs55932059

chr6-53005205-C-Achr6-53005205-C-Gchr6-53005205-C-T

Variant summary

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

The NM_014920.5(CILK1):c.1843G>T(p.Ala615Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. A615T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CILK1 NM_014920.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.732

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=0.08251417).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CILK1	NM_014920.5	c.1843G>T	p.Ala615Ser	missense_variant	14/14	ENST00000676107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CILK1	ENST00000676107.1	c.1843G>T	p.Ala615Ser	missense_variant	14/14		NM_014920.5	P1
CILK1	ENST00000350082.10	c.1864G>T	p.Ala622Ser	missense_variant	14/14	1
CILK1	ENST00000356971.3	c.1843G>T	p.Ala615Ser	missense_variant	15/15	2		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251174 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135814

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461854 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	15
Dann	Uncertain	1.0
DEOGEN2	Benign	0.0053	T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.011
FATHMM_MKL	Benign	0.53	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.083	T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	0.97	D;D
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.26	N;N
REVEL	Benign	0.22
Sift	Benign	0.097	T;T
Sift4G	Uncertain	0.025	D;D
Polyphen		0.015	B;B
Vest4		0.20
MutPred		0.14		Gain of glycosylation at A615 (P = 0.0038);Gain of glycosylation at A615 (P = 0.0038);
MVP		0.73
MPC		0.23
ClinPred		0.42	T
GERP RS		6.0
Varity_R		0.048
gMVP		0.21

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: rs55932059; hg19: chr6-52870003;