Variant 12-57093187-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005967.4(NAB2):c.1268A>C(p.His423Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000777 in 1,287,792 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.8e-7 ( 0 hom. )

Consequence

NAB2
NM_005967.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.00

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]

NAB2 links:

NAB2 (HGNC:):

NAB2 links:

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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	Protein	UniProt
NAB2	NM_005967.4 linkuse as main transcript	c.1268A>C	p.His423Pro	missense_variant	5/7	ENST00000300131.8	NP_005958.1	Q15742-1
NAB2	NM_001330305.2 linkuse as main transcript	c.1268A>C	p.His423Pro	missense_variant	5/6		NP_001317234.1	Q15742-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NAB2	ENST00000300131.8 linkuse as main transcript	c.1268A>C	p.His423Pro	missense_variant	5/7	1	NM_005967.4	ENSP00000300131.3	Q15742-1
NAB2	ENST00000342556.6 linkuse as main transcript	c.1268A>C	p.His423Pro	missense_variant	5/6	5		ENSP00000341491.6	Q15742-3
NAB2	ENST00000554839.1 linkuse as main transcript	n.*41A>C		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000412

AC:

AN:

242606

Hom.:

AF XY:

0.00000761

AC XY:

AN XY:

131430

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000336

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.77e-7

AC:

AN:

1287792

Hom.:

Cov.:

AF XY:

0.00000156

AC XY:

AN XY:

638980

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:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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 submitter

clinical testing

Ambry Genetics

Aug 31, 2022

The c.1268A>C (p.H423P) alteration is located in exon 5 (coding exon 5) of the NAB2 gene. This alteration results from a A to C substitution at nucleotide position 1268, causing the histidine (H) at amino acid position 423 to be replaced by a proline (P). 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

0.084

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Pathogenic

0.14

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.14

T;.

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.49

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.60

N;N

REVEL

Benign

0.22

Sift

Benign

0.11

.;T

Sift4G

Benign

0.24

T;T

Polyphen

0.92

P;.

Vest4

0.69

MutPred

0.25

Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);

MVP

0.76

MPC

2.1

ClinPred

0.36

GERP RS

5.0

Varity_R

0.44

gMVP

0.37

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over