Variant 9-93124916-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004148.4(NINJ1):c.451C>G(p.Gln151Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000656 in 152,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Consequence

NINJ1
NM_004148.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.45

Variant links:

Genes affected

NINJ1 (HGNC:7824): (ninjurin 1) The ninjurin protein is upregulated after nerve injury both in dorsal root ganglion neurons and in Schwann cells (Araki and Milbrandt, 1996 [PubMed 8780658]). It demonstrates properties of a homophilic adhesion molecule and promotes neurite outgrowth from primary cultured dorsal root ganglion neurons.[supplied by OMIM, Aug 2009]

NINJ1 links:

NINJ1 (HGNC:):

NINJ1 links:

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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=0.11523998).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NINJ1	NM_004148.4 linkuse as main transcript	c.451C>G	p.Gln151Glu	missense_variant	3/4	ENST00000375446.5	NP_004139.2	Q92982
NINJ1	XM_011518716.2 linkuse as main transcript	c.301C>G	p.Gln101Glu	missense_variant	4/5		XP_011517018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NINJ1	ENST00000375446.5 linkuse as main transcript	c.451C>G	p.Gln151Glu	missense_variant	3/4	1	NM_004148.4	ENSP00000364595.4	Q92982
NINJ1	ENST00000461162.5 linkuse as main transcript	n.510C>G		non_coding_transcript_exon_variant	4/5	2
NINJ1	ENST00000470314.5 linkuse as main transcript	n.419C>G		non_coding_transcript_exon_variant	3/4	3
NINJ1	ENST00000489274.1 linkuse as main transcript	n.1275C>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152232

Hom.:

Cov.:

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:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152350

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Feb 10, 2022

The c.451C>G (p.Q151E) alteration is located in exon 3 (coding exon 3) of the NINJ1 gene. This alteration results from a C to G substitution at nucleotide position 451, causing the glutamine (Q) at amino acid position 151 to be replaced by a glutamic acid (E). 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

Benign

0.075

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.095

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.48

M_CAP

Benign

0.0060

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.84

REVEL

Benign

0.080

Sift

Uncertain

0.029

Sift4G

Uncertain

0.052

Polyphen

0.0090

Vest4

0.12

MutPred

0.19

Gain of stability (P = 0.0318);

MVP

0.42

MPC

0.56

ClinPred

0.43

GERP RS

3.2

Varity_R

0.085

gMVP

0.78

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