Genetic Variant JRKL:p.Ser305Thr (chr11-96391562-T-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001261833.2(JRKL):c.913T>A(p.Ser305Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000211 in 1,419,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

JRKL
NM_001261833.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.84

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2750963).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JRKL	NM_001261833.2 link	c.913T>A	p.Ser305Thr	missense_variant	Exon 2 of 2	ENST00000332349.5	NP_001248762.1	Q9Y4A0
JRKL	NM_003772.4 link	c.913T>A	p.Ser305Thr	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.913T>A	p.Ser305Thr	missense_variant	Exon 2 of 2	2	NM_001261833.2	ENSP00000333350.4		Q9Y4A0
JRKL	ENST00000546177.1 link	n.85+1489T>A		intron_variant	Intron 1 of 2	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000163

AC:

AN:

184112

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000333

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:

0.00000211

AC:

AN:

1419366

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

702592

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31900

American (AMR)

AF:

0.00

AC:

AN:

37966

Ashkenazi Jewish (ASJ)

AF:

0.0000392

AC:

AN:

25484

East Asian (EAS)

AF:

0.00

AC:

AN:

36496

South Asian (SAS)

AF:

0.00

AC:

AN:

81766

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1089770

Other (OTH)

AF:

0.0000340

AC:

AN:

58864

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000168

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 07, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.913T>A (p.S305T) alteration is located in exon 1 (coding exon 1) of the JRKL gene. This alteration results from a T to A substitution at nucleotide position 913, causing the serine (S) at amino acid position 305 to be replaced by a threonine (T). 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

Benign

0.13

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.054

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.76

M_CAP

Benign

0.014

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.8

PhyloP100

3.8

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.6

REVEL

Benign

0.16

Sift

Uncertain

0.019

Sift4G

Uncertain

0.019

Polyphen

1.0

Vest4

0.38

MutPred

0.52

Loss of stability (P = 0.0687);

MVP

0.68

ClinPred

0.69

GERP RS

4.6

Varity_R

0.17

gMVP

0.75

Mutation Taster

=78/22

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

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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