rs782496497

Variant names:

• chr8-142664818-G-A
• NM_003724.4:c.1241C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-142664818-G-A
• chr8-142664818-G-C
• chr8-142664818-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_003724.4(JRK):​c.1241C>T​(p.Ser414Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,446,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/13 in silico tools predict 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: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: JRK NM_003724.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25

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.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity JERKY_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13386467).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JRK	NM_003724.4	c.1241C>T	p.Ser414Phe	missense_variant	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.1241C>T	p.Ser414Phe	missense_variant	Exon 2 of 2	2	NM_003724.4	ENSP00000482410.1
JRK	ENST00000614134.1	c.1241C>T	p.Ser414Phe	missense_variant	Exon 2 of 2	1		ENSP00000485390.1
JRK	ENST00000571961.7	c.1241C>T	p.Ser414Phe	missense_variant	Exon 2 of 3	1		ENSP00000461610.1
JRK	ENST00000615982.4	c.1241C>T	p.Ser414Phe	missense_variant	Exon 2 of 4	1		ENSP00000483808.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000277 AC: 4 AN: 1446306 Hom.: 0 Cov.: 34 AF XY: 0.00000557 AC XY: 4 AN XY: 718674

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: 0.00000362

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
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Benign	0.72
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.58	.;T;.;T
MetaRNN	Benign	0.13	T;T;T;T
PrimateAI	Benign	0.36	T
Sift4G	Uncertain	0.045	D;D;D;D
Vest4		0.091
MVP		0.54
GERP RS		3.7
Varity_R		0.12
gMVP		0.43

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: chr8-143746237;