rs148585549

Variant names:

• chr3-131723514-T-A
• NM_130808.3:c.292A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-131723514-T-A
• chr3-131723514-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_130808.3(CPNE4):​c.292A>T​(p.Ile98Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. I98S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CPNE4 NM_130808.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.22

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.77

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPNE4	NM_130808.3	c.292A>T	p.Ile98Phe	missense_variant	Exon 3 of 16	ENST00000429747.6	NP_570720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPNE4	ENST00000429747.6	c.292A>T	p.Ile98Phe	missense_variant	Exon 3 of 16	1	NM_130808.3	ENSP00000411904.1
CPNE4	ENST00000511604.5	c.292A>T	p.Ile98Phe	missense_variant	Exon 6 of 19	1		ENSP00000423811.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461674 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727122

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T;.;T;.;T;.;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D;.;.;.;.;D
M_CAP	Benign	0.054	D
MetaRNN	Pathogenic	0.77	D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Pathogenic	3.2	M;.;M;.;M;.;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.9	D;.;D;D;D;D;D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0020	D;.;D;D;D;D;D
Sift4G	Uncertain	0.014	D;D;D;D;D;D;D
Polyphen		0.27	B;B;B;B;B;B;.
Vest4		0.90
MutPred		0.47		Gain of disorder (P = 0.1774);.;Gain of disorder (P = 0.1774);.;Gain of disorder (P = 0.1774);.;Gain of disorder (P = 0.1774);
MVP		0.65
MPC		0.61
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.67
gMVP		0.59

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-131442358;