rs1177521463

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_032492.4(JAGN1):​c.46G>A​(p.Asp16Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,458,276 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

JAGN1
NM_032492.4 missense

Scores

9
7
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.65
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.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.95

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
JAGN1NM_032492.4 linkc.46G>A p.Asp16Asn missense_variant Exon 1 of 2 ENST00000647897.1 NP_115881.3 Q8N5M9
JAGN1NM_001363890.1 linkc.-223G>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
JAGN1ENST00000647897.1 linkc.46G>A p.Asp16Asn missense_variant Exon 1 of 2 NM_032492.4 ENSP00000496942.1 Q8N5M9
JAGN1ENST00000489724.2 linkc.46G>A p.Asp16Asn missense_variant Exon 1 of 2 3 ENSP00000497724.1 A0A3B3ITE9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1458276
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
725198
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.93
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Benign
-0.090
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.86
D;.;D
Eigen
Pathogenic
0.92
Eigen_PC
Pathogenic
0.88
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.93
.;D;D
M_CAP
Benign
0.074
D
MetaRNN
Pathogenic
0.95
D;D;D
MetaSVM
Uncertain
0.26
D
MutationAssessor
Pathogenic
3.1
M;.;M
PrimateAI
Uncertain
0.76
T
PROVEAN
Pathogenic
-4.7
D;.;.
REVEL
Uncertain
0.59
Sift
Pathogenic
0.0
D;.;.
Sift4G
Pathogenic
0.0
D;.;.
Polyphen
1.0
D;.;D
Vest4
0.93
MutPred
0.90
Gain of MoRF binding (P = 0.0251);Gain of MoRF binding (P = 0.0251);Gain of MoRF binding (P = 0.0251);
MVP
0.83
MPC
0.76
ClinPred
1.0
D
GERP RS
5.9
Varity_R
0.90
gMVP
0.70

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.

Other links and lift over

hg19: chr3-9932452; COSMIC: COSV57062560; API