chr10-35569111-C-A

Variant names:

• chr10-35569111-C-A
• NM_145012.6:c.967C>A

Variant summary

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

The NM_145012.6(CCNY):​c.967C>A​(p.Arg323Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCNY NM_145012.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.50

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=0.2708885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNY	NM_145012.6	c.967C>A	p.Arg323Ser	missense_variant	Exon 10 of 10	ENST00000374704.8	NP_659449.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNY	ENST00000374704.8	c.967C>A	p.Arg323Ser	missense_variant	Exon 10 of 10	1	NM_145012.6	ENSP00000363836.4
CCNY	ENST00000339497.7	c.892C>A	p.Arg298Ser	missense_variant	Exon 9 of 9	1		ENSP00000344275.5
CCNY	ENST00000265375.13	c.805C>A	p.Arg269Ser	missense_variant	Exon 11 of 11	1		ENSP00000265375.9
CCNY	ENST00000374706.5	c.805C>A	p.Arg269Ser	missense_variant	Exon 12 of 12	1		ENSP00000363838.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.967C>A (p.R323S) alteration is located in exon 10 (coding exon 10) of the CCNY gene. This alteration results from a C to A substitution at nucleotide position 967, causing the arginine (R) at amino acid position 323 to be replaced by a serine (S). 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	Pathogenic	0.93
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	.;T;.;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.94	.;D;D;D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.27	T;T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.4	.;M;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.7	D;D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Uncertain	0.0090	D;D;D;D
Polyphen		0.76, 0.94	.;P;.;P
Vest4		0.34
MutPred		0.30		.;Gain of phosphorylation at R323 (P = 0.0041);.;.;
MVP		0.60
MPC		0.98
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.67
gMVP		0.75

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-35858039;