dbSNP rs1258379215: NECAP1:p.Ala26Asp (chr12-8082365-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015509.4(NECAP1):c.77C>A(p.Ala26Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. A26V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NECAP1
NM_015509.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.68

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:

ENSG00000284697 (HGNC:):

ENSG00000284697 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3704741).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECAP1	NM_015509.4 link	c.77C>A	p.Ala26Asp	missense_variant	Exon 1 of 8	ENST00000339754.11	NP_056324.2	Q8NC96-1
NECAP1	NR_024260.2 link	n.92C>A		non_coding_transcript_exon_variant	Exon 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECAP1	ENST00000339754.11 link	c.77C>A	p.Ala26Asp	missense_variant	Exon 1 of 8	1	NM_015509.4	ENSP00000341737.5		Q8NC96-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461422

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726936

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Benign

-0.047

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;T;.;.;.;.

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Benign

0.75

LIST_S2

Pathogenic

0.98

.;D;D;D;D;D

M_CAP

Benign

0.070

MetaRNN

Benign

0.37

T;T;T;T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.9

M;M;.;.;.;.

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-2.9

.;D;.;.;.;D

REVEL

Benign

0.14

Sift

Benign

0.060

.;T;.;.;.;T

Sift4G

Benign

0.14

.;T;.;.;.;T

Polyphen

0.64

P;P;.;.;.;.

Vest4

0.54

MutPred

0.48

Gain of catalytic residue at P24 (P = 2e-04);Gain of catalytic residue at P24 (P = 2e-04);Gain of catalytic residue at P24 (P = 2e-04);Gain of catalytic residue at P24 (P = 2e-04);Gain of catalytic residue at P24 (P = 2e-04);Gain of catalytic residue at P24 (P = 2e-04);

MVP

0.65

MPC

1.2

ClinPred

0.99

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.74

gMVP

0.51

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

Computational scores

Splicing

Publications

Other links and lift over