Genetic Variant NM_015175.3:c.37C>T (chr3-46979898-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.813

Publications

0 publications found

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]

NBEAL2 links:

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]

CCDC12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015175.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBEAL2	NM_015175.3	MANE Select	c.37C>T	p.Leu13Phe	missense	Exon 1 of 54	NP_055990.1	Q6ZNJ1-1
	CCDC12	NM_144716.6		c.-73+2034G>A		intron	N/A	NP_653317.2	J3KR35

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NBEAL2	ENST00000450053.8	TSL:2 MANE Select	c.37C>T	p.Leu13Phe	missense	Exon 1 of 54	ENSP00000415034.2	Q6ZNJ1-1
NBEAL2	ENST00000933460.1		c.37C>T	p.Leu13Phe	missense	Exon 1 of 52	ENSP00000603519.1
NBEAL2	ENST00000952756.1		c.37C>T	p.Leu13Phe	missense	Exon 1 of 52	ENSP00000622815.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

305296

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

167774

African (AFR)

AF:

0.00

AC:

AN:

7618

American (AMR)

AF:

0.00

AC:

AN:

14876

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12026

East Asian (EAS)

AF:

0.00

AC:

AN:

20900

South Asian (SAS)

AF:

0.00

AC:

AN:

20464

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25828

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1510

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

184536

Other (OTH)

AF:

0.00

AC:

AN:

17538

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Gray platelet syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.013

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.73

M_CAP

Pathogenic

0.93

MetaRNN

Uncertain

0.53

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.4

PhyloP100

0.81

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-2.1

REVEL

Benign

0.20

Sift

Benign

0.045

Polyphen

0.99

Vest4

0.35

MutPred

0.24

Gain of methylation at K18 (P = 0.0832)

MVP

0.18

MPC

0.68

ClinPred

0.85

GERP RS

3.0

PromoterAI

0.0031

Neutral

(source)

Varity_R

0.26

gMVP

0.069

Mutation Taster

=78/22

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