chr12-57091127-C-G

Variant names:

• chr12-57091127-C-G
• NM_005967.4:c.86C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005967.4(NAB2):​c.86C>G​(p.Pro29Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAB2 NM_005967.4 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.23
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07682684).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005967.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAB2	NM_005967.4	MANE Select	c.86C>G	p.Pro29Arg	missense splice_region	Exon 2 of 7	NP_005958.1	Q15742-1
	NAB2	NM_001330305.2		c.86C>G	p.Pro29Arg	missense splice_region	Exon 2 of 6	NP_001317234.1	Q15742-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAB2	ENST00000300131.8	TSL:1 MANE Select	c.86C>G	p.Pro29Arg	missense splice_region	Exon 2 of 7	ENSP00000300131.3	Q15742-1
	NAB2	ENST00000953388.1		c.86C>G	p.Pro29Arg	missense splice_region	Exon 2 of 7	ENSP00000623447.1
	NAB2	ENST00000862010.1		c.86C>G	p.Pro29Arg	missense splice_region	Exon 2 of 7	ENSP00000532069.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.2
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.074
Sift	Benign	0.037	D
Sift4G	Benign	0.12	T
Polyphen		0.0010	B
Vest4		0.28
MutPred		0.20		Loss of loop (P = 0.0022)
MVP		0.20
MPC		1.0
ClinPred		0.13	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.33
gMVP		0.22
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr12-57484910;