rs369271997

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6

The NM_015909.4(NBAS):​c.5129C>T​(p.Thr1710Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000565 in 1,609,346 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

NBAS
NM_015909.4 missense

Scores

8
11

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 3.41
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;
BP6
Variant 2-15287082-G-A is Benign according to our data. Variant chr2-15287082-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 431716.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NBASNM_015909.4 linkuse as main transcriptc.5129C>T p.Thr1710Met missense_variant 42/52 ENST00000281513.10 NP_056993.2 A2RRP1-1G1UI26

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NBASENST00000281513.10 linkuse as main transcriptc.5129C>T p.Thr1710Met missense_variant 42/521 NM_015909.4 ENSP00000281513.5 A2RRP1-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152210
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251420
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000597
AC:
87
AN:
1457136
Hom.:
0
Cov.:
31
AF XY:
0.0000607
AC XY:
44
AN XY:
725248
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:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000713
Gnomad4 OTH exome
AF:
0.0000830
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152210
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000378
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Short stature-optic atrophy-Pelger-HuC+t anomaly syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterresearchTIDEX, University of British Columbia-- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 19, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
T
Eigen
Uncertain
0.26
Eigen_PC
Benign
0.19
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.79
T
M_CAP
Benign
0.021
T
MetaRNN
Uncertain
0.67
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.1
M
PrimateAI
Benign
0.37
T
PROVEAN
Uncertain
-2.8
D
REVEL
Benign
0.12
Sift
Uncertain
0.021
D
Sift4G
Uncertain
0.011
D
Polyphen
0.93
P
Vest4
0.64
MVP
0.52
MPC
0.11
ClinPred
0.85
D
GERP RS
3.7
Varity_R
0.059
gMVP
0.51

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: rs369271997; hg19: chr2-15427206; API