16-89695679-G-C

Variant names:

• chr16-89695679-G-C
• rs772157816
• NM_052988.5:c.1070G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2 PM5 BP4

The NM_052988.5(CDK10):​c.1070G>C​(p.Arg357Pro) variant causes a missense change involving the alteration of a 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R357H) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDK10 NM_052988.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.45

Genes affected

CDK10 (HGNC:1770): (cyclin dependent kinase 10) The protein encoded by this gene belongs to the CDK subfamily of the Ser/Thr protein kinase family. The CDK subfamily members are highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2, and are known to be essential for cell cycle progression. This kinase has been shown to play a role in cellular proliferation and its function is limited to cell cycle G2-M phase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr16-89695679-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 402152.We mark this variant Likely_pathogenic, oryginal submissions are: {Pathogenic=1, Likely_pathogenic=1, Uncertain_significance=1}.
• BP4: Computational evidence support a benign effect (MetaRNN=0.36706203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK10	NM_052988.5	c.1070G>C	p.Arg357Pro	missense_variant	Exon 13 of 13	ENST00000353379.12	NP_443714.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK10	ENST00000353379.12	c.1070G>C	p.Arg357Pro	missense_variant	Exon 13 of 13	1	NM_052988.5	ENSP00000338673.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0075	T;T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.83	T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.2	.;M
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.34	N;N
REVEL	Uncertain	0.35
Sift	Uncertain	0.0040	D;T
Sift4G	Uncertain	0.037	D;T
Polyphen		0.99	.;D
Vest4		0.57
MutPred		0.35		.;Loss of MoRF binding (P = 2e-04);
MVP		0.64
MPC		0.62
ClinPred		0.84	D
GERP RS		4.9
Varity_R		0.37
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs772157816; hg19: chr16-89762087;