12-38730326-T-A

Variant names:

• chr12-38730326-T-A
• rs202081373
• NM_153634.3:c.755A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153634.3(CPNE8):​c.755A>T​(p.Tyr252Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000201 in 1,445,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: CPNE8 NM_153634.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.74

Genes affected

CPNE8 (HGNC:23498): (copine 8) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.197213).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPNE8	NM_153634.3	c.755A>T	p.Tyr252Phe	missense_variant	Exon 11 of 20	ENST00000331366.10	NP_705898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPNE8	ENST00000331366.10	c.755A>T	p.Tyr252Phe	missense_variant	Exon 11 of 20	1	NM_153634.3	ENSP00000329748.5
CPNE8	ENST00000360449.3	c.719A>T	p.Tyr240Phe	missense_variant	Exon 11 of 20	2		ENSP00000353633.3
CPNE8	ENST00000551855.1	n.263A>T		non_coding_transcript_exon_variant	Exon 4 of 5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000121 AC: 3 AN: 248244 Hom.: 0 AF XY: 0.00000744 AC XY: 1 AN XY: 134360

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000999

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000888

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000201 AC: 29 AN: 1445044 Hom.: 0 Cov.: 26 AF XY: 0.0000208 AC XY: 15 AN XY: 719772

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000772

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000246

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.000223 Hom.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Benign	0.88
DEOGEN2	Benign	0.050	T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	0.023
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.048
Sift	Benign	0.61	T;T
Sift4G	Benign	0.54	T;T
Polyphen		0.0010	B;.
Vest4		0.45
MutPred		0.29		Gain of sheet (P = 0.0827);.;
MVP		0.40
MPC		0.33
ClinPred		0.19	T
GERP RS		4.4
Varity_R		0.16
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs202081373; hg19: chr12-39124128;