12-566066-C-A

Variant names:

• chr12-566066-C-A
• rs770915895
• NM_016533.6:c.146G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016533.6(NINJ2):​c.146G>T​(p.Arg49Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NINJ2 NM_016533.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.83
• Publications: 1 publications found

Genes affected

NINJ2 (HGNC:7825): (ninjurin 2) The protein encoded by this gene belongs to the ninjurin (for nerve injury induced) family. It is a cell surface adhesion protein that is upregulated in Schwann cells surrounding the distal segment of injured nerve, and promotes neurite outgrowth, thus may have a role in nerve regeneration after nerve injury. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36235616).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016533.6. 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
	NINJ2	NM_016533.6	MANE Select	c.146G>T	p.Arg49Leu	missense	Exon 2 of 4	NP_057617.3
	NINJ2	NM_001294345.2		c.125G>T	p.Arg42Leu	missense	Exon 2 of 4	NP_001281274.1	F8WBZ3
	NINJ2	NM_001294346.2		c.38G>T	p.Arg13Leu	missense	Exon 2 of 4	NP_001281275.1	F5H3L1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NINJ2	ENST00000305108.10	TSL:1 MANE Select	c.146G>T	p.Arg49Leu	missense	Exon 2 of 4	ENSP00000307552.5	Q9NZG7
	NINJ2	ENST00000662884.1		c.284G>T	p.Arg95Leu	missense	Exon 2 of 4	ENSP00000499548.1	A0A590UJR9
	NINJ2	ENST00000857849.1		c.146G>T	p.Arg49Leu	missense	Exon 2 of 3	ENSP00000527908.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

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	0.26
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.069
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.1	T
PhyloP100		3.8
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.093
Sift	Benign	0.051	T
Sift4G	Benign	0.10	T
Vest4		0.61
MVP		0.48
MPC		0.63
ClinPred		0.97	D
GERP RS		1.9
gMVP		0.76
Mutation Taster		=60/40	polymorphism

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

Other links and lift over

dbSNP: rs770915895; hg19: chr12-675232;