5-132747583-C-A

Variant names:

• chr5-132747583-C-A
• rs1358841098
• NM_001039780.4:c.88C>A

Variant summary

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

The NM_001039780.4(CCNI2):​c.88C>A​(p.Leu30Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000201 in 1,495,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: CCNI2 NM_001039780.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0430
• Publications: 0 publications found

Genes affected

CCNI2 (HGNC:33869): (cyclin I family member 2) Predicted to enable cyclin-dependent protein serine/threonine kinase regulator activity. Predicted to be involved in mitotic cell cycle phase transition and regulation of cyclin-dependent protein serine/threonine kinase activity. Predicted to be part of cyclin-dependent protein kinase holoenzyme complex. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.08475259).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039780.4. 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
	CCNI2	NM_001039780.4	MANE Select	c.88C>A	p.Leu30Met	missense	Exon 1 of 6	NP_001034869.1	Q6ZMN8-1
	CCNI2	NM_001287252.2		c.88C>A	p.Leu30Met	missense	Exon 1 of 6	NP_001274181.1	Q6ZMN8-2
	CCNI2	NM_001287253.2		c.88C>A	p.Leu30Met	missense	Exon 1 of 6	NP_001274182.1	Q6ZMN8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNI2	ENST00000378731.6	TSL:1 MANE Select	c.88C>A	p.Leu30Met	missense	Exon 1 of 6	ENSP00000368005.1	Q6ZMN8-1
	CCNI2	ENST00000614847.1	TSL:1	c.88C>A	p.Leu30Met	missense	Exon 1 of 6	ENSP00000478257.1	Q6ZMN8-2
	CCNI2	ENST00000878149.1		c.88C>A	p.Leu30Met	missense	Exon 1 of 6	ENSP00000548208.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152236 Hom.: 0 Cov.: 32

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000149 AC: 2 AN: 1343688 Hom.: 0 Cov.: 31 AF XY: 0.00000151 AC XY: 1 AN XY: 662402

African (AFR) AF: 0.00 AC: 0 AN: 27332

American (AMR) AF: 0.00 AC: 0 AN: 30990

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23662

East Asian (EAS) AF: 0.00 AC: 0 AN: 30428

South Asian (SAS) AF: 0.00 AC: 0 AN: 75152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5040

European-Non Finnish (NFE) AF: 0.00000189 AC: 2 AN: 1060974

Other (OTH) AF: 0.00 AC: 0 AN: 55852

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152236 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74370

African (AFR) AF: 0.00 AC: 0 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

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	0.098
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.043
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.023
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.94	P
Vest4		0.14
MutPred		0.20		Gain of phosphorylation at T33 (P = 0.144)
MVP		0.048
MPC		1.5
ClinPred		0.20	T
GERP RS		0.078
PromoterAI		0.076	Neutral
Varity_R		0.16
gMVP		0.075
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1358841098; hg19: chr5-132083275;