10-35516524-A-T

Variant names:

• chr10-35516524-A-T
• rs199787431
• NM_145012.6:c.266A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145012.6(CCNY):​c.266A>T​(p.His89Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000137 in 1,458,744 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H89P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCNY NM_145012.6 missense, splice_region
• Scores: Splicing: ADA: 0.004654
• Clinical Significance: Not reported in ClinVar
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19254133).

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>T	p.His89Leu	missense splice_region	Exon 4 of 10	NP_659449.3
	CCNY	NM_001282852.2		c.191A>T	p.His64Leu	missense splice_region	Exon 3 of 9	NP_001269781.1	Q8ND76-2
	CCNY	NM_001282853.2		c.104A>T	p.His35Leu	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>T	p.His89Leu	missense splice_region	Exon 4 of 10	ENSP00000363836.4	Q8ND76-1
	CCNY	ENST00000339497.7	TSL:1	c.191A>T	p.His64Leu	missense splice_region	Exon 3 of 9	ENSP00000344275.5	Q8ND76-2
	CCNY	ENST00000265375.13	TSL:1	c.104A>T	p.His35Leu	missense splice_region	Exon 5 of 11	ENSP00000265375.9	Q8ND76-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458744 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725996

African (AFR) AF: 0.00 AC: 0 AN: 33412

American (AMR) AF: 0.00 AC: 0 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109390

Other (OTH) AF: 0.0000166 AC: 1 AN: 60264

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Benign	0.90
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.14
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		5.1
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.17
Sift	Benign	0.35	T
Sift4G	Benign	0.72	T
Polyphen		0.0	B
Vest4		0.72
MutPred		0.29		Loss of disorder (P = 0.059)
MVP		0.31
MPC		0.85
ClinPred		0.57	D
GERP RS		6.0
Varity_R		0.18
gMVP		0.62
Mutation Taster		=47/53	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0047
dbscSNV1_RF	Benign	0.024
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

dbSNP: rs199787431; hg19: chr10-35805452;