chr12-663365-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016533.6(NINJ2):​c.-5G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,614,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

NINJ2
NM_016533.6 5_prime_UTR

Scores

4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.82
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21096343).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NINJ2NM_016533.6 linkc.-5G>A 5_prime_UTR_variant Exon 1 of 4 ENST00000305108.10 NP_057617.3 Q9NZG7A0A590UJR9B4DJC1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NINJ2ENST00000305108.10 linkc.-5G>A 5_prime_UTR_variant Exon 1 of 4 1 NM_016533.6 ENSP00000307552.5 Q9NZG7
NINJ2ENST00000662884.1 linkc.134G>A p.Ser45Asn missense_variant Exon 1 of 4 ENSP00000499548.1 A0A590UJR9
NINJ2-AS1ENST00000543884.2 linkn.258C>T non_coding_transcript_exon_variant Exon 3 of 3 3
NINJ2-AS1ENST00000662519.1 linkn.501C>T non_coding_transcript_exon_variant Exon 3 of 3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152228
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000637
AC:
16
AN:
251116
Hom.:
0
AF XY:
0.0000810
AC XY:
11
AN XY:
135738
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000141
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000157
AC:
23
AN:
1461864
Hom.:
0
Cov.:
31
AF XY:
0.0000206
AC XY:
15
AN XY:
727232
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:
0.0000189
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152228
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000377
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.000123
AC:
15

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 04, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.134G>A (p.S45N) alteration is located in exon 1 (coding exon 1) of the NINJ2 gene. This alteration results from a G to A substitution at nucleotide position 134, causing the serine (S) at amino acid position 45 to be replaced by an asparagine (N). 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
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
18
DANN
Uncertain
0.99
Eigen
Uncertain
0.26
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Benign
0.65
D
LIST_S2
Benign
0.34
T
M_CAP
Benign
0.0073
T
MetaRNN
Benign
0.21
T
MetaSVM
Benign
-0.94
T
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.64
N
REVEL
Benign
0.13
Sift
Uncertain
0.021
D
Sift4G
Benign
0.31
T
Vest4
0.13
MVP
0.74
MPC
0.18
ClinPred
0.78
D
GERP RS
4.8
gMVP
0.12

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.

Other links and lift over

dbSNP: rs759410413; hg19: chr12-772531; API