Variant 12-57091246-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_005967.4(NAB2):c.205G>A(p.Val69Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,450,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NAB2
NM_005967.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.80

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.893

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAB2	NM_005967.4 linkuse as main transcript	c.205G>A	p.Val69Met	missense_variant	2/7	ENST00000300131.8	NP_005958.1	Q15742-1
NAB2	NM_001330305.2 linkuse as main transcript	c.205G>A	p.Val69Met	missense_variant	2/6		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.205G>A	p.Val69Met	missense_variant	2/7	1	NM_005967.4	ENSP00000300131.3	Q15742-1
NAB2	ENST00000342556.6 linkuse as main transcript	c.205G>A	p.Val69Met	missense_variant	2/6	5		ENSP00000341491.6	Q15742-3
NAB2	ENST00000554718.1 linkuse as main transcript	n.221G>A		non_coding_transcript_exon_variant	2/2	5
NAB2	ENST00000555857.1 linkuse as main transcript	n.328G>A		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1450240

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719108

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.06e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 23, 2024

The c.205G>A (p.V69M) alteration is located in exon 2 (coding exon 2) of the NAB2 gene. This alteration results from a G to A substitution at nucleotide position 205, causing the valine (V) at amino acid position 69 to be replaced by a methionine (M). 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

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.78

D;.

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

1.0

D;D

M_CAP

Uncertain

0.20

MetaRNN

Pathogenic

0.89

D;D

MetaSVM

Uncertain

0.55

MutationAssessor

Uncertain

2.0

M;M

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-2.7

D;D

REVEL

Pathogenic

0.78

Sift

Uncertain

0.0010

.;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

1.0

D;.

Vest4

0.75

MutPred

0.77

Gain of catalytic residue at V69 (P = 0.0626);Gain of catalytic residue at V69 (P = 0.0626);

MVP

0.84

MPC

2.0

ClinPred

0.98

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.80

gMVP

0.87

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over