rs782252872

Variant names:

• chr8-142664761-C-A
• rs782252872
• NM_003724.4:c.1298G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-142664761-C-A
• chr8-142664761-C-G
• chr8-142664761-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003724.4(JRK):​c.1298G>T​(p.Arg433Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000163 in 1,590,442 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R433H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: JRK NM_003724.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.562
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0858891).

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.1298G>T	p.Arg433Leu	missense	Exon 2 of 2	NP_003715.3	O75564-2
	JRK	NM_001077527.3		c.1298G>T	p.Arg433Leu	missense	Exon 2 of 3	NP_001070995.2	O75564-1
	JRK	NM_001279352.2		c.1298G>T	p.Arg433Leu	missense	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.1298G>T	p.Arg433Leu	missense	Exon 2 of 2	ENSP00000482410.1	O75564-2
	JRK	ENST00000614134.1	TSL:1	c.1298G>T	p.Arg433Leu	missense	Exon 2 of 2	ENSP00000485390.1	O75564-2
	JRK	ENST00000571961.7	TSL:1	c.1298G>T	p.Arg433Leu	missense	Exon 2 of 3	ENSP00000461610.1	O75564-1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152118 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 200306 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000167 AC: 24 AN: 1438324 Hom.: 0 Cov.: 36 AF XY: 0.0000126 AC XY: 9 AN XY: 713310

African (AFR) AF: 0.00 AC: 0 AN: 32976

American (AMR) AF: 0.00 AC: 0 AN: 41172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25648

East Asian (EAS) AF: 0.00 AC: 0 AN: 38532

South Asian (SAS) AF: 0.00 AC: 0 AN: 82846

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.0000209 AC: 23 AN: 1101296

Other (OTH) AF: 0.0000168 AC: 1 AN: 59588

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152118 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74306

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2088

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0296732), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	0.26
DANN	Benign	0.59
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.41	T
MetaRNN	Benign	0.086	T
PhyloP100		-0.56
PrimateAI	Benign	0.26	T
Sift4G	Benign	0.39	T
Vest4		0.078
MVP		0.55
GERP RS		-4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.062
gMVP		0.25

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: rs782252872; hg19: chr8-143746180;