chr16-89686796-G-C

Variant names:

• chr16-89686796-G-C
• rs375838804
• NM_052988.5:c.86G>C

Variant summary

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

The NM_052988.5(CDK10):​c.86G>C​(p.Arg29Thr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000687 in 1,456,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CDK10 NM_052988.5 missense, splice_region
• Scores: Splicing: ADA: 0.7875
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.74

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]

LINC02166 (HGNC:53027): (long intergenic non-protein coding RNA 2166)

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=0.38622174).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK10	NM_052988.5	c.86G>C	p.Arg29Thr	missense_variant, splice_region_variant	Exon 1 of 13	ENST00000353379.12	NP_443714.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK10	ENST00000353379.12	c.86G>C	p.Arg29Thr	missense_variant, splice_region_variant	Exon 1 of 13	1	NM_052988.5	ENSP00000338673.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000426 AC: 1 AN: 234922 Hom.: 0 AF XY: 0.00000777 AC XY: 1 AN XY: 128676

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: 0.0000335

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456134 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724294

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: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	23
DANN	Benign	0.94
DEOGEN2	Benign	0.0090	T;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.052
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.87	D;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.97	L;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.80	N;.
REVEL	Benign	0.21
Sift	Benign	0.55	T;.
Sift4G	Benign	0.51	T;D
Polyphen		0.14	B;.
Vest4		0.63
MutPred		0.43		Gain of phosphorylation at R29 (P = 0.0197);Gain of phosphorylation at R29 (P = 0.0197);
MVP		0.51
MPC		0.15
ClinPred		0.45	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.35
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.79
dbscSNV1_RF	Benign	0.63
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: rs375838804; hg19: chr16-89753204;