rs776290356

Variant names:

• chr14-99510563-A-C
• rs776290356
• NM_001099402.2:c.1524A>C
• CCNK p.Pro508Pro

Your query was ambiguous. Multiple possible variants found:

• chr14-99510563-A-C
• chr14-99510563-A-G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001099402.2(CCNK):​c.1524A>C​(p.Pro508Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000063 (0 hom., cov: 6)
  • Exomes 𝑓: 0.000075 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCNK NM_001099402.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.896
• Publications: 0 publications found

Genes affected

CCNK (HGNC:1596): (cyclin K) The protein encoded by this gene is a member of the transcription cyclin family. These cyclins may regulate transcription through their association with and activation of cyclin-dependent kinases (CDK) that phosphorylate the C-terminal domain (CTD) of the large subunit of RNA polymerase II. This gene product may play a dual role in regulating CDK and RNA polymerase II activities. [provided by RefSeq, Jul 2008]

CCDC85C (HGNC:35459): (coiled-coil domain containing 85C) Predicted to be involved in cerebral cortex development. Located in adherens junction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 14-99510563-A-C is Benign according to our data. Variant chr14-99510563-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 402507.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.896 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099402.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNK	NM_001099402.2	MANE Select	c.1524A>C	p.Pro508Pro	synonymous	Exon 11 of 11	NP_001092872.1	O75909-3
	CCDC85C	NM_001144995.2	MANE Select	c.*4683T>G		3_prime_UTR	Exon 6 of 6	NP_001138467.1	A6NKD9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNK	ENST00000389879.9	TSL:5 MANE Select	c.1524A>C	p.Pro508Pro	synonymous	Exon 11 of 11	ENSP00000374529.5	O75909-3
	CCDC85C	ENST00000380243.9	TSL:5 MANE Select	c.*4683T>G		3_prime_UTR	Exon 6 of 6	ENSP00000369592.4	A6NKD9
	CCNK	ENST00000555049.5	TSL:1	c.1117+3416A>C		intron	N/A	ENSP00000452307.1	G3V5E1

Frequencies

GnomAD3 genomes AF: 0.0000632 AC: 2 AN: 31668 Hom.: 0 Cov.: 6

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000114

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000377 AC: 23 AN: 60938 AF XY: 0.000408

Gnomad AFR exome AF: 0.000210

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000483

Gnomad EAS exome AF: 0.000138

Gnomad FIN exome AF: 0.00178

Gnomad NFE exome AF: 0.000851

Gnomad OTH exome AF: 0.000503

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000753 AC: 15 AN: 199280 Hom.: 0 Cov.: 2 AF XY: 0.0000634 AC XY: 7 AN XY: 110442

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 5708

American (AMR) AF: 0.00 AC: 0 AN: 15038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4922

East Asian (EAS) AF: 0.000131 AC: 1 AN: 7650

South Asian (SAS) AF: 0.0000489 AC: 2 AN: 40894

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 680

European-Non Finnish (NFE) AF: 0.000114 AC: 12 AN: 105576

Other (OTH) AF: 0.00 AC: 0 AN: 9652

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000632 AC: 2 AN: 31668 Hom.: 0 Cov.: 6 AF XY: 0.000136 AC XY: 2 AN XY: 14684

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 6738

American (AMR) AF: 0.00 AC: 0 AN: 2912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1012

East Asian (EAS) AF: 0.00 AC: 0 AN: 776

South Asian (SAS) AF: 0.00 AC: 0 AN: 428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 56

European-Non Finnish (NFE) AF: 0.000114 AC: 2 AN: 17572

Other (OTH) AF: 0.00 AC: 0 AN: 420

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.4
DANN	Benign	0.69
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs776290356; hg19: chr14-99976900;