rs2976399

Variant names:

• chr8-142664633-T-A
• rs2976399
• NM_003724.4:c.1426A>T

Your query was ambiguous. Multiple possible variants found:

• chr8-142664633-T-A
• chr8-142664633-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003724.4(JRK):​c.1426A>T​(p.Arg476*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: JRK NM_003724.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730

Genes affected

JRK (HGNC:6199): (Jrk helix-turn-helix protein) This gene encodes a conserved protein that is similar to DNA-binding proteins, such as major centromere autoantigen B (CENPB). Inactivation of the related gene in mice resulted in epileptic seizures. Childhood Absence Epilepsy (CAE) has been mapped to the same chromosomal location (8q24.3) as this gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JRK	NM_003724.4	c.1426A>T	p.Arg476*	stop_gained	Exon 2 of 2	ENST00000612905.2	NP_003715.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JRK	ENST00000612905.2	c.1426A>T	p.Arg476*	stop_gained	Exon 2 of 2	2	NM_003724.4	ENSP00000482410.1
JRK	ENST00000614134.1	c.1426A>T	p.Arg476*	stop_gained	Exon 2 of 2	1		ENSP00000485390.1
JRK	ENST00000571961.7	c.1426A>T	p.Arg476*	stop_gained	Exon 2 of 3	1		ENSP00000461610.1
JRK	ENST00000615982.4	c.1426A>T	p.Arg476*	stop_gained	Exon 2 of 4	1		ENSP00000483808.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1458472 Hom.: 0 Cov.: 65 AF XY: 0.00 AC XY: 0 AN XY: 725452

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Pathogenic	33
Vest4		0.41

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

Other links and lift over

dbSNP: rs2976399; hg19: -;