dbSNP rs1490172529: JRKL:p.Arg7His (chr11-96390669-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001261833.2(JRKL):c.20G>A(p.Arg7His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

JRKL
NM_001261833.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.08

Publications

0 publications found

Variant links:

Genes affected

JRKL (HGNC:6200): (JRK like) The function of this gene has not yet been defined, however, the encoded protein shares similarity with the human (41% identical) and mouse (34% identical) jerky gene products. This protein may act as a nuclear regulatory protein. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, May 2012]

JRKL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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
JRKL	NM_001261833.2 link	c.20G>A	p.Arg7His	missense_variant	Exon 2 of 2	ENST00000332349.5	NP_001248762.1	Q9Y4A0
JRKL	NM_003772.4 link	c.20G>A	p.Arg7His	missense_variant	Exon 1 of 1		NP_003763.2	Q9Y4A0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JRKL	ENST00000332349.5 link	c.20G>A	p.Arg7His	missense_variant	Exon 2 of 2	2	NM_001261833.2	ENSP00000333350.4		Q9Y4A0
JRKL	ENST00000546177.1 link	n.85+596G>A		intron_variant	Intron 1 of 2	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000444

AC:

AN:

224976

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000349

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1433930

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712734

African (AFR)

AF:

0.00

AC:

AN:

31662

American (AMR)

AF:

0.00

AC:

AN:

37652

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24256

East Asian (EAS)

AF:

0.00

AC:

AN:

39622

South Asian (SAS)

AF:

0.00

AC:

AN:

81108

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52424

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5584

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102562

Other (OTH)

AF:

0.00

AC:

AN:

59060

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 01, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.20G>A (p.R7H) alteration is located in exon 1 (coding exon 1) of the JRKL gene. This alteration results from a G to A substitution at nucleotide position 20, causing the arginine (R) at amino acid position 7 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.044

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-0.37

MutationAssessor

Benign

1.8

PhyloP100

3.1

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.40

Sift

Benign

0.19

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.20

MutPred

0.84

Gain of sheet (P = 0.0221);

MVP

0.85

ClinPred

0.94

GERP RS

3.5

Varity_R

0.095

gMVP

0.77

Mutation Taster

=79/21

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over