NM_145012.6:c.266A>C

Variant names:

• chr10-35516524-A-C
• NM_145012.6:c.266A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145012.6(CCNY):​c.266A>C​(p.His89Pro) 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. 15/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H89R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCNY NM_145012.6 missense, splice_region
• Scores: Splicing: ADA: 0.5455
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.06
• Publications: 0 publications found

Genes affected

CCNY (HGNC:23354): (cyclin Y) Cyclins, such as CCNY, control cell division cycles and regulate cyclin-dependent kinases (e.g., CDC2; MIM 116940) (Li et al., 2009 [PubMed 18060517]).[supplied by OMIM, May 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34161207).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145012.6. 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
	CCNY	NM_145012.6	MANE Select	c.266A>C	p.His89Pro	missense splice_region	Exon 4 of 10	NP_659449.3
	CCNY	NM_001282852.2		c.191A>C	p.His64Pro	missense splice_region	Exon 3 of 9	NP_001269781.1	Q8ND76-2
	CCNY	NM_001282853.2		c.104A>C	p.His35Pro	missense splice_region	Exon 5 of 11	NP_001269782.1	Q8ND76-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNY	ENST00000374704.8	TSL:1 MANE Select	c.266A>C	p.His89Pro	missense splice_region	Exon 4 of 10	ENSP00000363836.4	Q8ND76-1
	CCNY	ENST00000339497.7	TSL:1	c.191A>C	p.His64Pro	missense splice_region	Exon 3 of 9	ENSP00000344275.5	Q8ND76-2
	CCNY	ENST00000265375.13	TSL:1	c.104A>C	p.His35Pro	missense splice_region	Exon 5 of 11	ENSP00000265375.9	Q8ND76-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.027	T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.1
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.14
Sift	Benign	0.28	T
Sift4G	Benign	0.21	T
Polyphen		0.080	B
Vest4		0.69
MutPred		0.42		Gain of disorder (P = 0.0513)
MVP		0.41
MPC		1.5
ClinPred		0.70	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.71
Mutation Taster		=46/54	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.55
dbscSNV1_RF	Benign	0.56
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

Other links and lift over

hg19: chr10-35805452;