Variant 12-8082371-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015509.4(NECAP1):c.83A>T(p.Asn28Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,014 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. N28N) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

NECAP1
NM_015509.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.96

Variant links:

Genes affected

NECAP1 (HGNC:24539): (NECAP endocytosis associated 1) This gene encodes a protein containing two characteristic WXXF motifs. The encoded protein localizes to clathrin-coated vesicles, where it binds components of the adapter protein complexes and aids in endocytosis. Loss of function of this gene results in early infantile epileptic encephalopathy-21. There is a pseudogene for this gene on chromosome 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

NECAP1 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	UniProt
NECAP1	NM_015509.4 linkuse as main transcript	c.83A>T	p.Asn28Ile	missense_variant	1/8	ENST00000339754.11
NECAP1	NR_024260.2 linkuse as main transcript	n.98A>T		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NECAP1	ENST00000339754.11 linkuse as main transcript	c.83A>T	p.Asn28Ile	missense_variant	1/8	1	NM_015509.4	P4	Q8NC96-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152014

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 21

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 24, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Uncertain

0.074

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;T;.;.;.;.

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.79

LIST_S2

Pathogenic

0.99

.;D;D;D;D;D

M_CAP

Uncertain

0.17

MetaRNN

Uncertain

0.72

D;D;D;D;D;D

MetaSVM

Benign

-0.61

MutationAssessor

Pathogenic

3.0

M;M;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-8.2

.;D;.;.;.;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.0020

.;D;.;.;.;D

Sift4G

Uncertain

0.0080

.;D;.;.;.;T

Polyphen

0.97

D;D;.;.;.;.

Vest4

0.84

MutPred

0.47

Gain of catalytic residue at P24 (P = 0);Gain of catalytic residue at P24 (P = 0);Gain of catalytic residue at P24 (P = 0);Gain of catalytic residue at P24 (P = 0);Gain of catalytic residue at P24 (P = 0);Gain of catalytic residue at P24 (P = 0);

MVP

0.67

MPC

1.5

ClinPred

1.0

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.92

gMVP

0.75

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over