rs370546877

Variant names:

• chr12-96283605-G-C
• rs370546877
• NM_002595.5:c.1363C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-96283605-G-C
• chr12-96283605-G-T

Variant summary

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

The NM_002595.5(CDK17):​c.1363C>G​(p.Gln455Glu) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. Q455K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CDK17 NM_002595.5 missense, splice_region
• Scores: Splicing: ADA: 0.7827
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.50

Genes affected

CDK17 (HGNC:8750): (cyclin dependent kinase 17) The protein encoded by this gene belongs to the cdc2/cdkx subfamily of the ser/thr family of protein kinases. It has similarity to a rat protein that is thought to play a role in terminally differentiated neurons. Alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, Jul 2010]

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=0.2986169).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK17	NM_002595.5	c.1363C>G	p.Gln455Glu	missense_variant, splice_region_variant	Exon 14 of 17	ENST00000261211.8	NP_002586.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK17	ENST00000261211.8	c.1363C>G	p.Gln455Glu	missense_variant, splice_region_variant	Exon 14 of 17	1	NM_002595.5	ENSP00000261211.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000405 AC: 1 AN: 246648 Hom.: 0 AF XY: 0.00000750 AC XY: 1 AN XY: 133308

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: 0.00000888

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.098	T;.;T
Eigen	Benign	-0.035
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.59	N;N;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.084
Sift	Benign	0.050	D;T;T
Sift4G	Benign	0.16	T;T;T
Polyphen		0.0030	B;.;.
Vest4		0.36
MutPred		0.31		Gain of ubiquitination at K459 (P = 0.0483);Gain of ubiquitination at K459 (P = 0.0483);.;
MVP		0.49
MPC		0.65
ClinPred		0.58	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.35
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.78
dbscSNV1_RF	Benign	0.55
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: rs370546877; hg19: chr12-96677383;