chr3-46979898-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015175.3(NBEAL2):​c.37C>T​(p.Leu13Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars). Synonymous variant affecting the same amino acid position (i.e. L13L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

NBEAL2
NM_015175.3 missense

Scores

1
6
11

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.813
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]
CCDC12 (HGNC:28332): (coiled-coil domain containing 12) Predicted to be part of U2-type spliceosomal complex and post-mRNA release spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NBEAL2NM_015175.3 linkuse as main transcriptc.37C>T p.Leu13Phe missense_variant 1/54 ENST00000450053.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NBEAL2ENST00000450053.8 linkuse as main transcriptc.37C>T p.Leu13Phe missense_variant 1/542 NM_015175.3 P2Q6ZNJ1-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
305296
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
167774
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Gray platelet syndrome Uncertain:1
Uncertain significance, no assertion criteria providedclinical testingZotz-Klimas Genetics Lab, MVZ Zotz KlimasOct 09, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Benign
-0.013
T
BayesDel_noAF
Benign
-0.26
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.055
T
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Benign
0.48
N
LIST_S2
Benign
0.73
T
M_CAP
Pathogenic
0.93
D
MetaRNN
Uncertain
0.53
D
MetaSVM
Benign
-0.64
T
MutationAssessor
Uncertain
2.4
M
MutationTaster
Benign
1.0
D;D;D;N
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.20
Sift
Benign
0.045
D
Polyphen
0.99
D
Vest4
0.35
MutPred
0.24
Gain of methylation at K18 (P = 0.0832);
MVP
0.18
MPC
0.68
ClinPred
0.85
D
GERP RS
3.0
Varity_R
0.26
gMVP
0.069

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-47021388; API