9-93125038-G-C

Variant names:

• chr9-93125038-G-C
• rs2275848
• NM_004148.4:c.329C>G

Variant summary

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

The NM_004148.4(NINJ1):​c.329C>G​(p.Ala110Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NINJ1 NM_004148.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84
• Publications: 49 publications found

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]

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=0.233248).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NINJ1	NM_004148.4	c.329C>G	p.Ala110Gly	missense_variant	Exon 3 of 4	ENST00000375446.5	NP_004139.2
NINJ1	XM_011518716.2	c.179C>G	p.Ala60Gly	missense_variant	Exon 4 of 5		XP_011517018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NINJ1	ENST00000375446.5	c.329C>G	p.Ala110Gly	missense_variant	Exon 3 of 4	1	NM_004148.4	ENSP00000364595.4
NINJ1	ENST00000461162.5	n.388C>G		non_coding_transcript_exon_variant	Exon 4 of 5	2
NINJ1	ENST00000470314.5	n.297C>G		non_coding_transcript_exon_variant	Exon 3 of 4	3
NINJ1	ENST00000489274.1	n.1153C>G		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461386 Hom.: 0 Cov.: 55 AF XY: 0.00000138 AC XY: 1 AN XY: 727002

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111758

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.089
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.8
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.14
Sift	Benign	0.34	T
Sift4G	Benign	0.32	T
Polyphen		0.94	P
Vest4		0.096
MutPred		0.50		Loss of helix (P = 0.0167);
MVP		0.61
MPC		0.58
ClinPred		0.70	D
GERP RS		2.5
Varity_R		0.093
gMVP		0.78
Mutation Taster		=88/12	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: rs2275848; hg19: chr9-95887320;