Variant 4-786634-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006651.4(CPLX1):c.272A>T(p.Glu91Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,416 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CPLX1
NM_006651.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.53

Variant links:

Genes affected

CPLX1 (HGNC:2309): (complexin 1) Proteins encoded by the complexin/synaphin gene family are cytosolic proteins that function in synaptic vesicle exocytosis. These proteins bind syntaxin, part of the SNAP receptor. The protein product of this gene binds to the SNAP receptor complex and disrupts it, allowing transmitter release. [provided by RefSeq, Jul 2008]

CPLX1 links:

CPLX1 (HGNC:):

CPLX1 links:

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ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
CPLX1	NM_006651.4 linkuse as main transcript	c.272A>T	p.Glu91Val	missense_variant	4/4	ENST00000304062.11	NP_006642.1	O14810
CPLX1	XM_011513391.2 linkuse as main transcript	c.227A>T	p.Glu76Val	missense_variant	3/3		XP_011511693.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CPLX1	ENST00000304062.11 linkuse as main transcript	c.272A>T	p.Glu91Val	missense_variant	4/4	1	NM_006651.4	ENSP00000305613.6	O14810
CPLX1	ENST00000505203.1 linkuse as main transcript	c.209A>T	p.Glu70Val	missense_variant	5/5	2		ENSP00000425960.1	D6RI11
CPLX1	ENST00000504062.1 linkuse as main transcript	c.227A>T	p.Glu76Val	missense_variant	3/3	3		ENSP00000421947.1	D6RAG3
CPLX1	ENST00000506404.1 linkuse as main transcript	n.325A>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460416

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726538

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 07, 2024

The c.272A>T (p.E91V) alteration is located in exon 4 (coding exon 3) of the CPLX1 gene. This alteration results from a A to T substitution at nucleotide position 272, causing the glutamic acid (E) at amino acid position 91 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Uncertain

0.049

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.40

T;.;.

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Pathogenic

0.35

MetaRNN

Uncertain

0.63

D;D;D

MetaSVM

Uncertain

-0.23

MutationAssessor

Uncertain

2.5

M;.;.

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Uncertain

0.29

Sift

Benign

0.056

T;T;T

Sift4G

Benign

0.16

T;T;T

Polyphen

0.99

D;D;.

Vest4

0.20

MutPred

0.63

Gain of glycosylation at T95 (P = 0.0084);.;.;

MVP

0.42

MPC

0.85

ClinPred

0.97

GERP RS

3.6

Varity_R

0.19

gMVP

0.63

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over