5-132752100-G-C

Variant names:

• chr5-132752100-G-C
• rs973245890
• NM_001039780.4:c.909G>C

Variant summary

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

The NM_001039780.4(CCNI2):​c.909G>C​(p.Lys303Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000828 in 1,448,624 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: CCNI2 NM_001039780.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.84
• 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]

SEPTIN8 (HGNC:16511): (septin 8) This gene is a member of the septin family of nucleotide binding proteins, originally described in yeast as cell division cycle regulatory proteins. Septins are highly conserved in yeast, Drosophila, and mouse, and appear to regulate cytoskeletal organization. Disruption of septin function disturbs cytokinesis and results in large multinucleate or polyploid cells. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.909G>C	p.Lys303Asn	missense	Exon 5 of 6	NP_001034869.1	Q6ZMN8-1
	SEPTIN8	NM_001098811.2	MANE Select	c.1368C>G	p.Pro456Pro	synonymous	Exon 10 of 10	NP_001092281.1	Q92599-1
	CCNI2	NM_001287252.2		c.957G>C	p.Lys319Asn	missense	Exon 5 of 6	NP_001274181.1	Q6ZMN8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNI2	ENST00000378731.6	TSL:1 MANE Select	c.909G>C	p.Lys303Asn	missense	Exon 5 of 6	ENSP00000368005.1	Q6ZMN8-1
	CCNI2	ENST00000614847.1	TSL:1	c.957G>C	p.Lys319Asn	missense	Exon 5 of 6	ENSP00000478257.1	Q6ZMN8-2
	SEPTIN8	ENST00000378719.7	TSL:1 MANE Select	c.1368C>G	p.Pro456Pro	synonymous	Exon 10 of 10	ENSP00000367991.2	Q92599-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000828 AC: 12 AN: 1448624 Hom.: 0 Cov.: 31 AF XY: 0.00000695 AC XY: 5 AN XY: 719104

African (AFR) AF: 0.00 AC: 0 AN: 33326

American (AMR) AF: 0.00 AC: 0 AN: 42898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25866

East Asian (EAS) AF: 0.00 AC: 0 AN: 39314

South Asian (SAS) AF: 0.00 AC: 0 AN: 83494

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.0000109 AC: 12 AN: 1105610

Other (OTH) AF: 0.00 AC: 0 AN: 59954

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.94
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.8
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.29
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.98	D
Vest4		0.58
MutPred		0.52		Loss of methylation at K303 (P = 0.0069)
MVP		0.45
MPC		0.52
ClinPred		0.98	D
GERP RS		4.1
Varity_R		0.53
gMVP		0.39
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs973245890; hg19: chr5-132087792;