chr9-93125038-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004148.4(NINJ1):​c.329C>A​(p.Ala110Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 1,613,308 control chromosomes in the GnomAD database, including 524,719 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 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: 𝑓 0.77 (45896 hom., cov: 32)
  • Exomes 𝑓: 0.81 (478823 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.656975E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004148.4. 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
	NINJ1	NM_004148.4	MANE Select	c.329C>A	p.Ala110Asp	missense	Exon 3 of 4	NP_004139.2	Q92982

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NINJ1	ENST00000375446.5	TSL:1 MANE Select	c.329C>A	p.Ala110Asp	missense	Exon 3 of 4	ENSP00000364595.4	Q92982
	NINJ1	ENST00000946696.1		c.428C>A	p.Ala143Asp	missense	Exon 3 of 4	ENSP00000616755.1
	NINJ1	ENST00000878645.1		c.422C>A	p.Ala141Asp	missense	Exon 4 of 5	ENSP00000548704.1

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117560 AN: 151972 Hom.: 45855 Cov.: 32

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.787

GnomAD2 exomes AF: 0.810 AC: 203167 AN: 250742 AF XY: 0.809

Gnomad AFR exome AF: 0.663

Gnomad AMR exome AF: 0.890

Gnomad ASJ exome AF: 0.788

Gnomad EAS exome AF: 0.890

Gnomad FIN exome AF: 0.773

Gnomad NFE exome AF: 0.801

Gnomad OTH exome AF: 0.804

GnomAD4 exome AF: 0.809 AC: 1182016 AN: 1461218 Hom.: 478823 Cov.: 55 AF XY: 0.809 AC XY: 587895 AN XY: 726910

African (AFR) AF: 0.665 AC: 22265 AN: 33474

American (AMR) AF: 0.882 AC: 39331 AN: 44608

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 20632 AN: 26110

East Asian (EAS) AF: 0.859 AC: 34064 AN: 39670

South Asian (SAS) AF: 0.816 AC: 70363 AN: 86180

European-Finnish (FIN) AF: 0.775 AC: 41376 AN: 53400

Middle Eastern (MID) AF: 0.807 AC: 4654 AN: 5764

European-Non Finnish (NFE) AF: 0.810 AC: 900974 AN: 1111658

Other (OTH) AF: 0.801 AC: 48357 AN: 60354

GnomAD4 genome AF: 0.774 AC: 117651 AN: 152090 Hom.: 45896 Cov.: 32 AF XY: 0.776 AC XY: 57671 AN XY: 74344

African (AFR) AF: 0.671 AC: 27826 AN: 41472

American (AMR) AF: 0.838 AC: 12804 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2746 AN: 3472

East Asian (EAS) AF: 0.886 AC: 4588 AN: 5176

South Asian (SAS) AF: 0.828 AC: 3990 AN: 4816

European-Finnish (FIN) AF: 0.774 AC: 8196 AN: 10584

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.807 AC: 54847 AN: 67974

Other (OTH) AF: 0.789 AC: 1667 AN: 2112

Alfa AF: 0.795 Hom.: 142116

Bravo AF: 0.775

TwinsUK AF: 0.801 AC: 2970

ALSPAC AF: 0.818 AC: 3152

ESP6500AA AF: 0.677 AC: 2981

ESP6500EA AF: 0.814 AC: 7000

ExAC AF: 0.804 AC: 97656

Asia WGS AF: 0.854 AC: 2965 AN: 3478

EpiCase AF: 0.802

EpiControl AF: 0.806

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.45	T
MetaRNN	Benign	9.7e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.8
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.15
Sift	Benign	0.54	T
Sift4G	Benign	0.52	T
Polyphen		0.94	P
Vest4		0.041
MPC		0.78
ClinPred		0.031	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.21
gMVP		0.91
Mutation Taster		=89/11	polymorphism (auto)

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; COSMIC: COSV64922551; COSMIC: COSV64922551;