GeneBe

rs765110272

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031232.4(NECAB3):​c.452G>T​(p.Ser151Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. S151N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

NECAB3
NM_031232.4 missense

Scores

1
6
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0750

Publications

0 publications found
Variant links:
Genes affected
NECAB3 (HGNC:15851): (N-terminal EF-hand calcium binding protein 3) The protein encoded by this gene interacts with the amino-terminal domain of the neuron-specific X11-like protein (X11L), inhibits the association of X11L with amyloid precursor protein through a non-competitive mechanism, and abolishes the suppression of beta-amyloid production by X11L. This protein, together with X11L, may play an important role in the regulatory system of amyloid precursor protein metabolism and beta-amyloid generation. The protein is phosphorylated by NIMA-related expressed kinase 2, and localizes to the Golgi apparatus. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.2608186).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031232.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
NECAB3
NM_031232.4
MANE Select
c.452G>Tp.Ser151Ile
missense
Exon 6 of 12NP_112509.3
NECAB3
NM_031231.4
c.452G>Tp.Ser151Ile
missense
Exon 6 of 13NP_112508.3

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
NECAB3
ENST00000246190.11
TSL:5 MANE Select
c.452G>Tp.Ser151Ile
missense
Exon 6 of 12ENSP00000246190.6Q96P71-1
NECAB3
ENST00000375238.8
TSL:1
c.452G>Tp.Ser151Ile
missense
Exon 6 of 13ENSP00000364386.4Q96P71-2
NECAB3
ENST00000883747.1
c.452G>Tp.Ser151Ile
missense
Exon 6 of 12ENSP00000553806.1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
T
Eigen
Uncertain
0.24
Eigen_PC
Benign
0.20
FATHMM_MKL
Benign
0.71
D
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.26
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.5
M
PhyloP100
0.075
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-4.2
D
REVEL
Benign
0.074
Sift
Uncertain
0.0010
D
Sift4G
Pathogenic
0.0010
D
Polyphen
0.95
P
Vest4
0.37
MutPred
0.35
Loss of disorder (P = 0.0016)
MVP
0.17
MPC
0.96
ClinPred
0.98
D
GERP RS
3.1
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
3.7
Varity_R
0.26
gMVP
0.48
Mutation Taster
=92/8
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

Publications

Other links and lift over

dbSNP: rs765110272; hg19: chr20-32248137; API