NM_032492.4:c.52C>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2

The NM_032492.4(JAGN1):​c.52C>T​(p.Gln18*) variant causes a stop gained change. 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 stop_gained

Scores

2
4
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.81
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.906 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
JAGN1NM_032492.4 linkc.52C>T p.Gln18* stop_gained Exon 1 of 2 ENST00000647897.1 NP_115881.3 Q8N5M9
JAGN1NM_001363890.1 linkc.-217C>T 5_prime_UTR_variant Exon 1 of 2 NP_001350819.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
JAGN1ENST00000647897.1 linkc.52C>T p.Gln18* stop_gained Exon 1 of 2 NM_032492.4 ENSP00000496942.1 Q8N5M9
JAGN1ENST00000489724.2 linkc.52C>T p.Gln18* stop_gained Exon 1 of 2 3 ENSP00000497724.1 A0A3B3ITE9

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
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.65
CADD
Pathogenic
38
DANN
Uncertain
1.0
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Uncertain
0.82
D
Vest4
0.22
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs200485958; hg19: chr3-9932458; API