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GeneBe

2-15167112-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015909.4(NBAS):ā€‹c.7052G>Cā€‹(p.Arg2351Thr) 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 1,461,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

NBAS
NM_015909.4 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.27
Variant links:
Genes affected
NBAS (HGNC:15625): (NBAS subunit of NRZ tethering complex) This gene encodes a protein with two leucine zipper domains, a ribosomal protein S14 signature domain and a Sec39 like domain. The protein is thought to be involved in Golgi-to-ER transport. Mutations in this gene are associated with short stature, optic nerve atrophy, and Pelger-Huet anomaly. [provided by RefSeq, Oct 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.39738238).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NBASNM_015909.4 linkuse as main transcriptc.7052G>C p.Arg2351Thr missense_variant 52/52 ENST00000281513.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NBASENST00000281513.10 linkuse as main transcriptc.7052G>C p.Arg2351Thr missense_variant 52/521 NM_015909.4 P1A2RRP1-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461456
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726980
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeMay 06, 2022This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 2351 of the NBAS protein (p.Arg2351Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NBAS-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Uncertain
0.026
T
BayesDel_noAF
Benign
-0.20
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.21
T;T
Eigen
Uncertain
0.28
Eigen_PC
Benign
0.21
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.91
D;D
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.40
T;T
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.6
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.31
T
PROVEAN
Uncertain
-2.5
N;D
REVEL
Benign
0.20
Sift
Uncertain
0.013
D;D
Sift4G
Uncertain
0.0070
D;D
Polyphen
0.91
P;.
Vest4
0.64
MutPred
0.44
Loss of MoRF binding (P = 0.0068);.;
MVP
0.37
MPC
0.15
ClinPred
0.95
D
GERP RS
3.5
Varity_R
0.14
gMVP
0.60

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: chr2-15307236; API