3-9890653-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032492.4(JAGN1):​c.-70G>T 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 0.00000152 in 1,311,808 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: JAGN1 NM_032492.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 0 publications found

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]

JAGN1 Gene-Disease associations (from GenCC):

• autosomal recessive severe congenital neutropenia due to JAGN1 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032492.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAGN1	NM_032492.4	MANE Select	c.-70G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	NP_115881.3
	JAGN1	NM_032492.4	MANE Select	c.-70G>T		5_prime_UTR	Exon 1 of 2	NP_115881.3
	JAGN1	NM_001363890.1		c.-338G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	NP_001350819.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAGN1	ENST00000647897.1	MANE Select	c.-70G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000496942.1	Q8N5M9
	JAGN1	ENST00000647897.1	MANE Select	c.-70G>T		5_prime_UTR	Exon 1 of 2	ENSP00000496942.1	Q8N5M9
	JAGN1	ENST00000915552.1		c.-70G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000585611.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000152 AC: 2 AN: 1311808 Hom.: 0 Cov.: 18 AF XY: 0.00000154 AC XY: 1 AN XY: 648602

African (AFR) AF: 0.00 AC: 0 AN: 29734

American (AMR) AF: 0.00 AC: 0 AN: 33390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23516

East Asian (EAS) AF: 0.00 AC: 0 AN: 35704

South Asian (SAS) AF: 0.0000132 AC: 1 AN: 75584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49100

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4606

European-Non Finnish (NFE) AF: 9.95e-7 AC: 1 AN: 1005392

Other (OTH) AF: 0.00 AC: 0 AN: 54782

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.3
DANN	Benign	0.75
PhyloP100		0.061
PromoterAI		-0.15	Neutral

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

Other links and lift over

dbSNP: rs279558; hg19: chr3-9932337;