8-142664633-T-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 19 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003724.4. 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
	JRK	NM_003724.4	MANE Select	c.1426A>T	p.Arg476*	stop_gained	Exon 2 of 2	NP_003715.3	O75564-2
	JRK	NM_001077527.3		c.1426A>T	p.Arg476*	stop_gained	Exon 2 of 3	NP_001070995.2	O75564-1
	JRK	NM_001279352.2		c.1426A>T	p.Arg476*	stop_gained	Exon 2 of 4	NP_001266281.1	O75564-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JRK	ENST00000612905.2	TSL:2 MANE Select	c.1426A>T	p.Arg476*	stop_gained	Exon 2 of 2	ENSP00000482410.1	O75564-2
	JRK	ENST00000614134.1	TSL:1	c.1426A>T	p.Arg476*	stop_gained	Exon 2 of 2	ENSP00000485390.1	O75564-2
	JRK	ENST00000571961.7	TSL:1	c.1426A>T	p.Arg476*	stop_gained	Exon 2 of 3	ENSP00000461610.1	O75564-1

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

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26034

East Asian (EAS) AF: 0.00 AC: 0 AN: 39634

South Asian (SAS) AF: 0.00 AC: 0 AN: 85800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51906

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111104

Other (OTH) AF: 0.00 AC: 0 AN: 60316

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Pathogenic	33
PhyloP100		-0.073
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

Other links and lift over

dbSNP: rs2976399;