rs751452713

Variant names:

• chr3-9890761-C-A
• rs751452713
• NM_032492.4:c.39C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-9890761-C-A
• chr3-9890761-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032492.4(JAGN1):​c.39C>A​(p.Asp13Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: JAGN1 NM_032492.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500

Genes affected

JAGN1 (HGNC:26926): (jagunal homolog 1) The protein encoded by this gene is a transmembrane protein. It functions in the early secretory pathway and is necessary for neutrophil differentiation and survival. Mutations in this gene result in severe congenital neutropenia. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.816

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAGN1	NM_032492.4	c.39C>A	p.Asp13Glu	missense_variant	Exon 1 of 2	ENST00000647897.1	NP_115881.3
JAGN1	NM_001363890.1	c.-230C>A		5_prime_UTR_variant	Exon 1 of 2		NP_001350819.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JAGN1	ENST00000647897.1	c.39C>A	p.Asp13Glu	missense_variant	Exon 1 of 2		NM_032492.4	ENSP00000496942.1
JAGN1	ENST00000489724.2	c.39C>A	p.Asp13Glu	missense_variant	Exon 1 of 2	3		ENSP00000497724.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.81	D;.;D
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.85	.;D;T
M_CAP	Benign	0.028	D
MetaRNN	Pathogenic	0.82	D;D;D
MetaSVM	Uncertain	-0.070	T
MutationAssessor	Pathogenic	3.0	M;.;M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.3	D;.;.
REVEL	Pathogenic	0.81
Sift	Uncertain	0.0050	D;.;.
Sift4G	Uncertain	0.012	D;.;.
Polyphen		1.0	D;.;D
Vest4		0.48
MutPred		0.65		Gain of MoRF binding (P = 0.0902);Gain of MoRF binding (P = 0.0902);Gain of MoRF binding (P = 0.0902);
MVP		0.75
MPC		0.29
ClinPred		0.99	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.73
gMVP		0.54

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

Other links and lift over

dbSNP: rs751452713; hg19: chr3-9932445;