chr12-57093118-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005967.4(NAB2):ā€‹c.1199A>Gā€‹(p.Tyr400Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000182 in 1,613,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000085 ( 0 hom., cov: 32)
Exomes š‘“: 0.00019 ( 0 hom. )

Consequence

NAB2
NM_005967.4 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.04
Variant links:
Genes affected
NAB2 (HGNC:7627): (NGFI-A binding protein 2) This gene encodes a member of the family of NGFI-A binding (NAB) proteins, which function in the nucleus to repress transcription induced by some members of the EGR (early growth response) family of transactivators. NAB proteins can homo- or hetero-multimerize with other EGR or NAB proteins through a conserved N-terminal domain, and repress transcription through two partially redundant C-terminal domains. Transcriptional repression by the encoded protein is mediated in part by interactions with the nucleosome remodeling and deactylase (NuRD) complex. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.13459289).
BS2
High AC in GnomAd4 at 13 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NAB2NM_005967.4 linkuse as main transcriptc.1199A>G p.Tyr400Cys missense_variant 5/7 ENST00000300131.8 NP_005958.1 Q15742-1
NAB2NM_001330305.2 linkuse as main transcriptc.1199A>G p.Tyr400Cys missense_variant 5/6 NP_001317234.1 Q15742-3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NAB2ENST00000300131.8 linkuse as main transcriptc.1199A>G p.Tyr400Cys missense_variant 5/71 NM_005967.4 ENSP00000300131.3 Q15742-1
NAB2ENST00000342556.6 linkuse as main transcriptc.1199A>G p.Tyr400Cys missense_variant 5/65 ENSP00000341491.6 Q15742-3
NAB2ENST00000554839.1 linkuse as main transcriptn.541A>G non_coding_transcript_exon_variant 3/33

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152156
Hom.:
0
Cov.:
32
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:
0.000176
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000152
AC:
38
AN:
250646
Hom.:
0
AF XY:
0.000170
AC XY:
23
AN XY:
135448
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000869
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000490
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000221
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000192
AC:
281
AN:
1461460
Hom.:
0
Cov.:
38
AF XY:
0.000175
AC XY:
127
AN XY:
727052
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000225
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152156
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74322
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:
0.000176
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000160
Hom.:
0
Bravo
AF:
0.000166
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.000140
AC:
17
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 13, 2023The c.1199A>G (p.Y400C) alteration is located in exon 5 (coding exon 5) of the NAB2 gene. This alteration results from a A to G substitution at nucleotide position 1199, causing the tyrosine (Y) at amino acid position 400 to be replaced by a cysteine (C). 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
0.073
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.13
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
T;.
Eigen
Benign
0.14
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.86
D;D
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.55
N;N
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
0.40
N;N
REVEL
Benign
0.11
Sift
Uncertain
0.016
.;D
Sift4G
Benign
0.17
T;T
Polyphen
0.92
P;.
Vest4
0.54
MVP
0.37
MPC
1.8
ClinPred
0.094
T
GERP RS
5.0
Varity_R
0.26
gMVP
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs147286767; hg19: chr12-57486901; API