3-46989279-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015175.3(NBEAL2):​c.371C>T​(p.Pro124Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,688 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NBEAL2
NM_015175.3 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0110
Variant links:
Genes affected
NBEAL2 (HGNC:31928): (neurobeachin like 2) The protein encoded by this gene contains a beige and Chediak-Higashi (BEACH) domain and multiple WD40 domains, and may play a role in megakaryocyte alpha-granule biogenesis. Mutations in this gene are a cause of gray platelet syndrome. [provided by RefSeq, Dec 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08317527).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NBEAL2NM_015175.3 linkuse as main transcriptc.371C>T p.Pro124Leu missense_variant 5/54 ENST00000450053.8 NP_055990.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NBEAL2ENST00000450053.8 linkuse as main transcriptc.371C>T p.Pro124Leu missense_variant 5/542 NM_015175.3 ENSP00000415034 P2Q6ZNJ1-1
NBEAL2ENST00000651747.1 linkuse as main transcriptc.350C>T p.Pro117Leu missense_variant 5/53 ENSP00000499216 A2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1458688
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
725376
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 21, 2022The c.371C>T (p.P124L) alteration is located in exon 5 (coding exon 5) of the NBEAL2 gene. This alteration results from a C to T substitution at nucleotide position 371, causing the proline (P) at amino acid position 124 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.066
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
3.5
DANN
Benign
0.75
DEOGEN2
Benign
0.026
T
Eigen
Benign
-0.88
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.60
T
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.083
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Uncertain
2.1
M
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.069
Sift
Benign
0.10
T
Polyphen
0.0
B
Vest4
0.18
MutPred
0.25
Loss of disorder (P = 0.0167);
MVP
0.18
MPC
0.19
ClinPred
0.069
T
GERP RS
1.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.12
gMVP
0.14

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs1225527977; hg19: chr3-47030769; API