Genetic Variant NBEA:p.Ser40Asn (chr13-34942939-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001385012.1(NBEA):c.119G>A(p.Ser40Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000318 in 1,572,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

NBEA
NM_001385012.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.064513475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBEA	NM_001385012.1 link	c.119G>A	p.Ser40Asn	missense_variant	Exon 1 of 59	ENST00000379939.7	NP_001371941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBEA	ENST00000379939.7 link	c.119G>A	p.Ser40Asn	missense_variant	Exon 1 of 59	5	NM_001385012.1	ENSP00000369271.2		Q5T321

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151378

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000970

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

GnomAD3 exomes

AF:

0.00000504

AC:

AN:

198580

Hom.:

AF XY:

0.00000906

AC XY:

AN XY:

110392

show subpopulations

Gnomad AFR exome

AF:

0.000101

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.04e-7

AC:

AN:

1420638

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

703654

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:

9.16e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151378

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73958

show subpopulations

Gnomad4 AFR

AF:

0.0000970

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:

0.0000113

ExAC

AF:

0.00000840

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.056

T;.;T;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.66

T;T;T;T

M_CAP

Benign

0.076

MetaRNN

Benign

0.065

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.;.;.

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.14

N;N;.;N

REVEL

Benign

0.062

Sift

Benign

0.087

T;T;.;T

Sift4G

Benign

0.13

T;T;T;T

Polyphen

0.0

.;.;.;B

Vest4

0.12

MutPred

0.23

Loss of glycosylation at S40 (P = 5e-04);Loss of glycosylation at S40 (P = 5e-04);Loss of glycosylation at S40 (P = 5e-04);Loss of glycosylation at S40 (P = 5e-04);

MVP

0.16

MPC

0.85

ClinPred

0.048

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.095

gMVP

0.54

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over