rs35283248

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003724.4(JRK):​c.1508G>T​(p.Arg503Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 9/13 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)

Consequence

JRK
NM_003724.4 missense

Scores

9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.80
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10471839).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
JRKNM_003724.4 linkc.1508G>T p.Arg503Leu missense_variant Exon 2 of 2 ENST00000612905.2 NP_003715.3 O75564-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
JRKENST00000612905.2 linkc.1508G>T p.Arg503Leu missense_variant Exon 2 of 2 2 NM_003724.4 ENSP00000482410.1 O75564-2
JRKENST00000614134.1 linkc.1508G>T p.Arg503Leu missense_variant Exon 2 of 2 1 ENSP00000485390.1 O75564-2
JRKENST00000571961.7 linkc.1508G>T p.Arg503Leu missense_variant Exon 2 of 3 1 ENSP00000461610.1 O75564-1
JRKENST00000615982.4 linkc.1508G>T p.Arg503Leu missense_variant Exon 2 of 4 1 ENSP00000483808.1 O75564-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000862
AC:
2
AN:
231884
Hom.:
0
AF XY:
0.0000157
AC XY:
2
AN XY:
127400
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000194
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.0000166
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
0.18
DANN
Benign
0.78
FATHMM_MKL
Benign
0.042
N
LIST_S2
Benign
0.68
.;T;.;T
MetaRNN
Benign
0.10
T;T;T;T
PrimateAI
Benign
0.43
T
Sift4G
Benign
0.24
T;T;T;T
Vest4
0.14
MVP
0.57
GERP RS
-1.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.076
gMVP
0.28

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35283248; hg19: chr8-143745968; API