11-96391062-T-G

Position:

• chr11-96391062-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001261833.2(JRKL):​c.413T>G​(p.Ile138Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: JRKL NM_001261833.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.31

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]

ACMG classification

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=0.22555944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JRKL	NM_001261833.2	c.413T>G	p.Ile138Ser	missense_variant	2/2	ENST00000332349.5
JRKL	NM_003772.4	c.413T>G	p.Ile138Ser	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JRKL	ENST00000332349.5	c.413T>G	p.Ile138Ser	missense_variant	2/2	2	NM_001261833.2	P1
JRKL	ENST00000546177.1	n.85+989T>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 11, 2023

The c.413T>G (p.I138S) alteration is located in exon 1 (coding exon 1) of the JRKL gene. This alteration results from a T to G substitution at nucleotide position 413, causing the isoleucine (I) at amino acid position 138 to be replaced by a serine (S). 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	0.23
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.063
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
MutationTaster	Benign	0.70	D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.095
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.51	P
Vest4		0.43
MutPred		0.47		Gain of disorder (P = 0.0052);
MVP		0.34
ClinPred		0.60	D
GERP RS		4.5
Varity_R		0.32
gMVP		0.72

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: chr11-96124226;