rs201239059

Variant names:

• chr3-131723537-C-T
• rs201239059
• NM_130808.3:c.269G>A

Variant summary

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

The NM_130808.3(CPNE4):​c.269G>A​(p.Arg90His) variant causes a missense change. The variant allele was found at a frequency of 0.000123 in 1,613,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: CPNE4 NM_130808.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.08
• Publications: 4 publications found

Genes affected

CPNE4 (HGNC:2317): (copine 4) This gene belongs to the highly conserved copine family. It encodes a calcium-dependent, phospholipid-binding protein, which may be involved in membrane trafficking, mitogenesis and development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130808.3. 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
	CPNE4	NM_130808.3	MANE Select	c.269G>A	p.Arg90His	missense	Exon 3 of 16	NP_570720.1	Q96A23-1
	CPNE4	NM_001289112.2		c.323G>A	p.Arg108His	missense	Exon 3 of 16	NP_001276041.1	Q96A23-2
	CPNE4	NM_153429.2		c.323G>A	p.Arg108His	missense	Exon 4 of 17	NP_702907.1	Q96A23-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPNE4	ENST00000429747.6	TSL:1 MANE Select	c.269G>A	p.Arg90His	missense	Exon 3 of 16	ENSP00000411904.1	Q96A23-1
	CPNE4	ENST00000512332.5	TSL:1	c.323G>A	p.Arg108His	missense	Exon 4 of 17	ENSP00000424853.1	Q96A23-2
	CPNE4	ENST00000511604.5	TSL:1	c.269G>A	p.Arg90His	missense	Exon 6 of 19	ENSP00000423811.1	Q96A23-1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152150 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

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: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000358 AC: 9 AN: 251472 AF XY: 0.0000294

Gnomad AFR exome AF: 0.000123

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: 0.0000615

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000125 AC: 183 AN: 1461734 Hom.: 0 Cov.: 30 AF XY: 0.000114 AC XY: 83 AN XY: 727158

African (AFR) AF: 0.0000597 AC: 2 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5668

European-Non Finnish (NFE) AF: 0.000157 AC: 175 AN: 1111972

Other (OTH) AF: 0.0000662 AC: 4 AN: 60390

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152150 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74310

African (AFR) AF: 0.000121 AC: 5 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68024

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

Alfa AF: 0.000154 Hom.: 1

Bravo AF: 0.000121

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

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	0.22
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.090	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	1.5	L
PhyloP100		6.1
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.46
Sift	Benign	0.033	D
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.72
MVP		0.50
MPC		1.0
ClinPred		0.54	D
GERP RS		5.2
Varity_R		0.35
gMVP		0.43
Mutation Taster		=69/31	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: rs201239059; hg19: chr3-131442381; COSMIC: COSV70199521; COSMIC: COSV70199521;