10-35516524-A-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/23 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

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

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=0.34161207).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNY	NM_145012.6	c.266A>C	p.His89Pro	missense_variant, splice_region_variant	Exon 4 of 10	ENST00000374704.8	NP_659449.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNY	ENST00000374704.8	c.266A>C	p.His89Pro	missense_variant, splice_region_variant	Exon 4 of 10	1	NM_145012.6	ENSP00000363836.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.266A>C (p.H89P) alteration is located in exon 4 (coding exon 4) of the CCNY gene. This alteration results from a A to C substitution at nucleotide position 266, causing the histidine (H) at amino acid position 89 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;.;T;T;.;.
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;.;D;D;D;D
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.34	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	.;.;.;L;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.6	.;N;.;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.28	.;T;.;T;T;T
Sift4G	Benign	0.21	T;T;T;T;T;T
Polyphen		0.080, 0.44	.;.;.;B;.;B
Vest4		0.69, 0.68, 0.69, 0.66
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-35805452;