rs569985954

Variant names:

• chr3-9890733-G-A
• NM_032492.4:c.11G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-9890733-G-A
• chr3-9890733-G-C
• chr3-9890733-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_032492.4(JAGN1):​c.11G>A​(p.Arg4Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,090 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: 6.9e-7 (0 hom.)
• Consequence: JAGN1 NM_032492.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.31

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.853

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAGN1	NM_032492.4	c.11G>A	p.Arg4Gln	missense_variant	Exon 1 of 2	ENST00000647897.1	NP_115881.3
JAGN1	NM_001363890.1	c.-258G>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.11G>A	p.Arg4Gln	missense_variant	Exon 1 of 2		NM_032492.4	ENSP00000496942.1
JAGN1	ENST00000489724.2	c.11G>A	p.Arg4Gln	missense_variant	Exon 1 of 2	3		ENSP00000497724.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456090 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723896

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: 9.01e-7

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	0.58
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.82	D;.;D
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	.;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.85	D;D;D
MetaSVM	Uncertain	-0.0036	T
MutationAssessor	Pathogenic	3.1	M;.;M
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.2	D;.;.
REVEL	Uncertain	0.41
Sift	Uncertain	0.010	D;.;.
Sift4G	Uncertain	0.010	D;.;.
Polyphen		1.0	D;.;D
Vest4		0.66
MutPred		0.74		Loss of MoRF binding (P = 6e-04);Loss of MoRF binding (P = 6e-04);Loss of MoRF binding (P = 6e-04);
MVP		0.76
MPC		0.85
ClinPred		0.98	D
GERP RS		4.2
Varity_R		0.58
gMVP		0.48

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: chr3-9932417; COSMIC: COSV105145538;