chr3-108560735-T-A

Variant names:

• chr3-108560735-T-A
• rs150480320
• NM_020890.3:c.1741A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020890.3(CIP2A):​c.1741A>T​(p.Ile581Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. I581V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CIP2A NM_020890.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.413
• Publications: 0 publications found

Genes affected

CIP2A (HGNC:29302): (cellular inhibitor of PP2A) Enables protein homodimerization activity. Predicted to act upstream of or within positive regulation of neural precursor cell proliferation and spermatogenesis. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028510243).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020890.3. 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
	CIP2A	NM_020890.3	MANE Select	c.1741A>T	p.Ile581Leu	missense	Exon 14 of 21	NP_065941.2	Q8TCG1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIP2A	ENST00000295746.13	TSL:1 MANE Select	c.1741A>T	p.Ile581Leu	missense	Exon 14 of 21	ENSP00000295746.7	Q8TCG1-1
	CIP2A	ENST00000491772.5	TSL:1	c.1264A>T	p.Ile422Leu	missense	Exon 14 of 21	ENSP00000419487.1	Q8TCG1-2
	CIP2A	ENST00000481530.5	TSL:1	n.*1311A>T		non_coding_transcript_exon	Exon 14 of 21	ENSP00000417297.1	F8WAX6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460008 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726416

African (AFR) AF: 0.00 AC: 0 AN: 33386

American (AMR) AF: 0.00 AC: 0 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.00 AC: 0 AN: 86188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110548

Other (OTH) AF: 0.00 AC: 0 AN: 60312

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.43
DANN	Benign	0.70
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.4	N
PhyloP100		-0.41
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.0070
Sift	Benign	0.72	T
Sift4G	Benign	0.81	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.25		Gain of ubiquitination at K582 (P = 0.0751)
MVP		0.24
MPC		0.15
ClinPred		0.038	T
GERP RS		-1.4
Varity_R		0.031
gMVP		0.18
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: rs150480320; hg19: chr3-108279582;