Genetic Variant NBEA:p.Gly7Asp (chr13-34942840-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001385012.1(NBEA):c.20G>A(p.Gly7Asp) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G7V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NBEA
NM_001385012.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55

Publications

0 publications found

Variant links:

Genes affected

NBEA (HGNC:7648): (neurobeachin) This gene encodes a member of a large, diverse group of A-kinase anchor proteins that target the activity of protein kinase A to specific subcellular sites by binding to its type II regulatory subunits. Brain-specific expression and coat protein-like membrane recruitment of a highly similar protein in mouse suggest an involvement in neuronal post-Golgi membrane traffic. Mutations in this gene may be associated with a form of autism. This gene and its expression are frequently disrupted in patients with multiple myeloma. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants may exist, but their full-length nature has not been determined.[provided by RefSeq, Feb 2011]

NBEA Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
neurodevelopmental disorder with or without early-onset generalized epilepsy
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
syndromic intellectual disability
Inheritance: AD Classification: STRONG Submitted by: Illumina

NBEA links:

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=0.07841948).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385012.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NBEA	NM_001385012.1	MANE Select	c.20G>A	p.Gly7Asp	missense	Exon 1 of 59	NP_001371941.1	Q5T321
NBEA	NM_001379245.1		c.20G>A	p.Gly7Asp	missense	Exon 1 of 58	NP_001366174.1
NBEA	NM_015678.5		c.20G>A	p.Gly7Asp	missense	Exon 1 of 58	NP_056493.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NBEA	ENST00000379939.7	TSL:5 MANE Select	c.20G>A	p.Gly7Asp	missense	Exon 1 of 59	ENSP00000369271.2	Q5T321
NBEA	ENST00000400445.8	TSL:5	c.20G>A	p.Gly7Asp	missense	Exon 1 of 58	ENSP00000383295.3	Q8NFP9-1
NBEA	ENST00000691351.1		c.20G>A	p.Gly7Asp	missense	Exon 1 of 22	ENSP00000509284.1	A0A8I5QKR6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1214034

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

589556

African (AFR)

AF:

0.00

AC:

AN:

23262

American (AMR)

AF:

0.00

AC:

AN:

12774

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16860

East Asian (EAS)

AF:

0.00

AC:

AN:

28620

South Asian (SAS)

AF:

0.00

AC:

AN:

56968

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33242

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3402

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

988790

Other (OTH)

AF:

0.00

AC:

AN:

50116

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

See cases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.064

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.74

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

PhyloP100

1.6

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.23

REVEL

Benign

0.077

Sift

Benign

0.081

Sift4G

Benign

0.14

Polyphen

0.013

Vest4

0.36

MutPred

0.20

Gain of solvent accessibility (P = 0.0216)

MVP

0.24

MPC

1.2

ClinPred

0.19

GERP RS

1.9

Varity_R

0.079

gMVP

0.72

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over