14-24073049-C-T

Variant names:

• chr14-24073049-C-T
• NM_006032.4:c.113C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006032.4(CPNE6):​c.113C>T​(p.Thr38Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,405,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CPNE6 NM_006032.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.535
• Publications: 0 publications found

Genes affected

CPNE6 (HGNC:2319): (copine 6) This gene encodes a member of the copine family. Members of this family are calcium-dependent, phospholipid-binding proteins with C2 domains, two calcium- and phospholipid-binding domains. Through their domain structure and lipid binding capabilities, these proteins may play a role in membrane trafficking. This protein is thought to be brain-specific and has a domain structure of two N-terminal C2 domains and one von Willebrand factor A domain. It may have a role in synaptic plasticity. [provided by RefSeq, Jul 2013]

DHRS4-AS1 (HGNC:23175): (DHRS4 antisense RNA 1)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25979525).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006032.4. 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
	CPNE6	NM_006032.4	MANE Select	c.113C>T	p.Thr38Ile	missense	Exon 2 of 17	NP_006023.1	O95741-1
	CPNE6	NM_001280558.2		c.278C>T	p.Thr93Ile	missense	Exon 3 of 18	NP_001267487.1	O95741-2
	CPNE6	NM_001385056.1		c.113C>T	p.Thr38Ile	missense	Exon 3 of 18	NP_001371985.1	O95741-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPNE6	ENST00000689861.1	MANE Select	c.113C>T	p.Thr38Ile	missense	Exon 2 of 17	ENSP00000510387.1	O95741-1
	CPNE6	ENST00000537691.5	TSL:2	c.278C>T	p.Thr93Ile	missense	Exon 3 of 18	ENSP00000440077.1	O95741-2
	CPNE6	ENST00000966862.1		c.113C>T	p.Thr38Ile	missense	Exon 2 of 17	ENSP00000636921.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.11e-7 AC: 1 AN: 1405834 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 697528

African (AFR) AF: 0.00 AC: 0 AN: 30264

American (AMR) AF: 0.00 AC: 0 AN: 37144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23356

East Asian (EAS) AF: 0.00 AC: 0 AN: 36052

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79368

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50648

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5208

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1086006

Other (OTH) AF: 0.00 AC: 0 AN: 57788

GnomAD4 genome Cov.: 32

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	0.21
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.42	N
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.54
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.060
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.25	B
Vest4		0.35
MutPred		0.48		Gain of catalytic residue at K39 (P = 0)
MVP		0.47
MPC		0.89
ClinPred		0.91	D
GERP RS		2.5
Varity_R		0.36
gMVP		0.49
Mutation Taster		=85/15	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

hg19: chr14-24542258;