rs786205704
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP3_ModeratePP5
The NM_032492.4(JAGN1):c.40G>A(p.Gly14Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G14D) has been classified as Uncertain significance.
Frequency
Consequence
NM_032492.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JAGN1 | NM_032492.4 | c.40G>A | p.Gly14Ser | missense_variant | 1/2 | ENST00000647897.1 | |
JAGN1 | NM_001363890.1 | c.-229G>A | 5_prime_UTR_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JAGN1 | ENST00000647897.1 | c.40G>A | p.Gly14Ser | missense_variant | 1/2 | NM_032492.4 | P1 | ||
JAGN1 | ENST00000489724.2 | c.40G>A | p.Gly14Ser | missense_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Severe congenital neutropenia Pathogenic:1
Pathogenic, criteria provided, single submitter | in vitro | Klein lab, Ludwig-Maximilians-University | Jan 01, 2013 | Neutropenia patients with mutations in JAGN1 respond poorly to treatment with recombinant human G-CSF - |
Autosomal recessive severe congenital neutropenia due to JAGN1 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 28, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change affects JAGN1 function (PMID: 33206996). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 190480). This missense change has been observed in individual(s) with JAGN1-related conditions (PMID: 25129144, 27980538, 33206996). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 14 of the JAGN1 protein (p.Gly14Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at