3-9890653-G-A

Variant names:

• chr3-9890653-G-A
• rs279558
• NM_032492.4:c.-70G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032492.4(JAGN1):​c.-70G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000615 in 1,463,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000061 (0 hom.)
• Consequence: JAGN1 NM_032492.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAGN1	NM_032492.4	c.-70G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	ENST00000647897.1	NP_115881.3
JAGN1	NM_032492.4	c.-70G>A		5_prime_UTR_variant	Exon 1 of 2	ENST00000647897.1	NP_115881.3
JAGN1	NM_001363890.1	c.-338G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2		NP_001350819.1
JAGN1	NM_001363890.1	c.-338G>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	c.-70G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2		NM_032492.4	ENSP00000496942.1
JAGN1	ENST00000647897	c.-70G>A		5_prime_UTR_variant	Exon 1 of 2		NM_032492.4	ENSP00000496942.1
JAGN1	ENST00000489724	c.-70G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	3		ENSP00000497724.1
JAGN1	ENST00000489724	c.-70G>A		5_prime_UTR_variant	Exon 1 of 2	3		ENSP00000497724.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151812 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000610 AC: 8 AN: 1311806 Hom.: 0 Cov.: 18 AF XY: 0.00000617 AC XY: 4 AN XY: 648600

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: 0.00000796

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151812 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74114

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.7
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs279558; hg19: chr3-9932337;