5-132747500-C-T

Variant names:

• chr5-132747500-C-T
• rs1403839750
• NM_001039780.4:c.5C>T

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.5C>T​(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000474 in 1,478,308 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: 0.0000045 (0 hom.)
• Consequence: CCNI2 NM_001039780.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.447
• 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=0.21717271).

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.5C>T	p.Ala2Val	missense	Exon 1 of 6	NP_001034869.1	Q6ZMN8-1
	CCNI2	NM_001287252.2		c.5C>T	p.Ala2Val	missense	Exon 1 of 6	NP_001274181.1	Q6ZMN8-2
	CCNI2	NM_001287253.2		c.5C>T	p.Ala2Val	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.5C>T	p.Ala2Val	missense	Exon 1 of 6	ENSP00000368005.1	Q6ZMN8-1
	CCNI2	ENST00000614847.1	TSL:1	c.5C>T	p.Ala2Val	missense	Exon 1 of 6	ENSP00000478257.1	Q6ZMN8-2
	CCNI2	ENST00000878149.1		c.5C>T	p.Ala2Val	missense	Exon 1 of 6	ENSP00000548208.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152088 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 89054 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000452 AC: 6 AN: 1326220 Hom.: 0 Cov.: 31 AF XY: 0.00000306 AC XY: 2 AN XY: 654274

African (AFR) AF: 0.00 AC: 0 AN: 26986

American (AMR) AF: 0.00 AC: 0 AN: 28486

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22232

East Asian (EAS) AF: 0.00 AC: 0 AN: 29574

South Asian (SAS) AF: 0.00 AC: 0 AN: 71824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5136

European-Non Finnish (NFE) AF: 0.00000569 AC: 6 AN: 1054000

Other (OTH) AF: 0.00 AC: 0 AN: 54776

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152088 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74298

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2092

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	0.34
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0036	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.45
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.10
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.26
MutPred		0.16		Loss of relative solvent accessibility (P = 0.0676)
MVP		0.20
MPC		1.6
ClinPred		0.64	D
GERP RS		3.3
PromoterAI		-0.12	Neutral
Varity_R		0.22
gMVP		0.17
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs1403839750; hg19: chr5-132083192;