6-36823096-T-G

Variant names:

• chr6-36823096-T-G
• NM_020939.2:c.98A>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020939.2(CPNE5):​c.98A>C​(p.Asn33Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,414,870 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. N33S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CPNE5 NM_020939.2 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22

Genes affected

CPNE5 (HGNC:2318): (copine 5) Calcium-dependent membrane-binding proteins may regulate molecular events at the interface of the cell membrane and cytoplasm. This gene is one of several genes that encode a calcium-dependent protein containing two N-terminal type II C2 domains and an integrin A domain-like sequence in the C-terminus. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. More variants may exist, but their full-length natures could not be determined. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPNE5	NM_020939.2	c.98A>C	p.Asn33Thr	missense_variant, splice_region_variant	Exon 2 of 21	ENST00000244751.7	NP_065990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPNE5	ENST00000244751.7	c.98A>C	p.Asn33Thr	missense_variant, splice_region_variant	Exon 2 of 21	1	NM_020939.2	ENSP00000244751.2
CPNE5	ENST00000633136.2	c.98A>C	p.Asn33Thr	missense_variant, splice_region_variant	Exon 2 of 22	5		ENSP00000487872.2
CPNE5	ENST00000633280.1	c.98A>C	p.Asn33Thr	missense_variant, splice_region_variant	Exon 2 of 10	5		ENSP00000488125.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.07e-7 AC: 1 AN: 1414870 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 701674

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000248

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

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	Uncertain	0.38
BayesDel_addAF	Benign	0.0083	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.48	T;T;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.63	T;T;T
M_CAP	Benign	0.072	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Pathogenic	3.7	H;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.8	D;.;.
REVEL	Uncertain	0.36
Sift	Uncertain	0.0060	D;.;.
Sift4G	Uncertain	0.015	D;D;D
Polyphen		0.96	D;.;.
Vest4		0.54
MutPred		0.51		Loss of stability (P = 0.0156);.;Loss of stability (P = 0.0156);
MVP		0.73
MPC		1.5
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.37
gMVP		0.40

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: chr6-36790872;