chr2-203049827-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001378026.1(NBEAL1):​c.157C>A​(p.Pro53Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,740 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. P53S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

NBEAL1
NM_001378026.1 missense

Scores

2
5
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.48

Publications

1 publications found
Variant links:
Genes affected
NBEAL1 (HGNC:20681): (neurobeachin like 1) Predicted to enable protein kinase binding activity. Predicted to be involved in protein localization. Predicted to be active in cytosol and membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.38984323).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NBEAL1NM_001378026.1 linkc.157C>A p.Pro53Thr missense_variant Exon 4 of 56 ENST00000683969.1 NP_001364955.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NBEAL1ENST00000683969.1 linkc.157C>A p.Pro53Thr missense_variant Exon 4 of 56 NM_001378026.1 ENSP00000508055.1 A0A804HKS6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.15e-7
AC:
1
AN:
1398740
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
689920
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
31828
American (AMR)
AF:
0.00
AC:
0
AN:
35620
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25086
East Asian (EAS)
AF:
0.00
AC:
0
AN:
36166
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79028
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
49444
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5690
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1077812
Other (OTH)
AF:
0.0000172
AC:
1
AN:
58066
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.69
BayesDel_addAF
Uncertain
0.054
T
BayesDel_noAF
Benign
-0.16
CADD
Uncertain
26
DANN
Benign
0.85
DEOGEN2
Benign
0.0089
T
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.058
D
MetaRNN
Benign
0.39
T
MetaSVM
Benign
-0.47
T
MutationAssessor
Benign
1.4
L
PhyloP100
7.5
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.29
Sift
Benign
0.47
T
Sift4G
Benign
0.67
T
Polyphen
0.99
D
Vest4
0.42
MutPred
0.42
Loss of disorder (P = 0.1059);
MVP
0.70
MPC
0.21
ClinPred
0.53
D
GERP RS
5.0
Varity_R
0.22
gMVP
0.68
Mutation Taster
=70/30
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs754292716; hg19: chr2-203914550; API