ENST00000505473.5:c.-164A>T

Variant names:

• chr16-89686722-A-T
• rs192221267
• ENST00000505473.5:c.-164A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000505473.5(CDK10):​c.-164A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00533 in 1,605,928 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0043 (3 hom., cov: 34)
  • Exomes 𝑓: 0.0054 (32 hom.)
• Consequence: CDK10 ENST00000505473.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.847
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 16-89686722-A-T is Benign according to our data. Variant chr16-89686722-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2570958.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00432 (657/152078) while in subpopulation NFE AF = 0.00669 (454/67866). AF 95% confidence interval is 0.00618. There are 3 homozygotes in GnomAd4. There are 306 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK10	NM_052988.5	c.12A>T	p.Pro4Pro	synonymous_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.12A>T	p.Pro4Pro	synonymous_variant	Exon 1 of 13	1	NM_052988.5	ENSP00000338673.7

Frequencies

GnomAD3 genomes AF: 0.00433 AC: 658 AN: 151960 Hom.: 3 Cov.: 34

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00536

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00425

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00669

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00413 AC: 963 AN: 232896 AF XY: 0.00420

Gnomad AFR exome AF: 0.0000718

Gnomad AMR exome AF: 0.00322

Gnomad ASJ exome AF: 0.00483

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00416

Gnomad NFE exome AF: 0.00606

Gnomad OTH exome AF: 0.00405

GnomAD4 exome AF: 0.00544 AC: 7908 AN: 1453850 Hom.: 32 Cov.: 31 AF XY: 0.00549 AC XY: 3967 AN XY: 722754

African (AFR) AF: 0.000451 AC: 15 AN: 33238

American (AMR) AF: 0.00302 AC: 133 AN: 44042

Ashkenazi Jewish (ASJ) AF: 0.00555 AC: 144 AN: 25940

East Asian (EAS) AF: 0.00 AC: 0 AN: 39128

South Asian (SAS) AF: 0.00230 AC: 196 AN: 85044

European-Finnish (FIN) AF: 0.00589 AC: 308 AN: 52288

Middle Eastern (MID) AF: 0.00436 AC: 25 AN: 5736

European-Non Finnish (NFE) AF: 0.00611 AC: 6769 AN: 1108432

Other (OTH) AF: 0.00530 AC: 318 AN: 60002

GnomAD4 genome AF: 0.00432 AC: 657 AN: 152078 Hom.: 3 Cov.: 34 AF XY: 0.00412 AC XY: 306 AN XY: 74348

African (AFR) AF: 0.000866 AC: 36 AN: 41548

American (AMR) AF: 0.00529 AC: 81 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4820

European-Finnish (FIN) AF: 0.00425 AC: 45 AN: 10594

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00669 AC: 454 AN: 67866

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00644 Hom.: 2

Bravo AF: 0.00406

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CDK10: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.64
PhyloP100		-0.85
PromoterAI		0.030	Neutral
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs192221267; hg19: chr16-89753130; COSMIC: COSV58414379; COSMIC: COSV58414379;