12-663365-C-G

Variant names:

• chr12-663365-C-G
• rs759410413
• NM_016533.6:c.-5G>C

Variant summary

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

The NM_016533.6(NINJ2):​c.-5G>C variant causes a 5 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NINJ2 NM_016533.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• Publications: 2 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]

NINJ2-AS1 (HGNC:40405): (NINJ2 antisense RNA 1)

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=0.21757105).

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.-5G>C		5_prime_UTR	Exon 1 of 4	NP_057617.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NINJ2	ENST00000305108.10	TSL:1 MANE Select	c.-5G>C		5_prime_UTR	Exon 1 of 4	ENSP00000307552.5	Q9NZG7
	NINJ2	ENST00000662884.1		c.134G>C	p.Ser45Thr	missense	Exon 1 of 4	ENSP00000499548.1	A0A590UJR9
	NINJ2	ENST00000857849.1		c.-5G>C		5_prime_UTR	Exon 1 of 3	ENSP00000527908.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251116 AF XY: 0.00000737

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.97
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.8
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.10
Sift	Benign	0.18	T
Sift4G	Benign	0.27	T
Vest4		0.11
MutPred		0.12		Loss of phosphorylation at S45 (P = 0.0458)
MVP		0.73
MPC		0.16
ClinPred		0.91	D
GERP RS		4.8
PromoterAI		0.029	Neutral
gMVP		0.16
Mutation Taster		=83/17	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: rs759410413; hg19: chr12-772531;