chr3-9890778-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_032492.4(JAGN1):​c.56A>C​(p.His19Pro) variant causes a missense 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 missense

Scores

5
7
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.05
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 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, 0.783

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
JAGN1NM_032492.4 linkc.56A>C p.His19Pro missense_variant Exon 1 of 2 ENST00000647897.1 NP_115881.3 Q8N5M9
JAGN1NM_001363890.1 linkc.-213A>C 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.56A>C p.His19Pro missense_variant Exon 1 of 2 NM_032492.4 ENSP00000496942.1 Q8N5M9
JAGN1ENST00000489724.2 linkc.56A>C p.His19Pro missense_variant Exon 1 of 2 3 ENSP00000497724.1 A0A3B3ITE9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000420
AC:
1
AN:
238224
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
129468
show subpopulations
Gnomad AFR exome
AF:
0.0000663
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000825
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.71
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.34
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.79
D;.;D
Eigen
Uncertain
0.21
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.84
.;T;T
M_CAP
Benign
0.0080
T
MetaRNN
Pathogenic
0.78
D;D;D
MetaSVM
Benign
-0.69
T
MutationAssessor
Benign
1.9
L;.;L
PrimateAI
Uncertain
0.77
T
PROVEAN
Pathogenic
-7.8
D;.;.
REVEL
Uncertain
0.52
Sift
Benign
0.051
T;.;.
Sift4G
Benign
0.065
T;.;.
Polyphen
0.20
B;.;B
Vest4
0.65
MutPred
0.69
Gain of loop (P = 0.0502);Gain of loop (P = 0.0502);Gain of loop (P = 0.0502);
MVP
0.58
MPC
0.33
ClinPred
0.82
D
GERP RS
5.9
Varity_R
0.93
gMVP
0.76

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs748123071; hg19: chr3-9932462; API