chr11-96391052-A-T

Variant names:

• chr11-96391052-A-T
• rs1378523836
• NM_001261833.2:c.403A>T

Variant summary

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

The NM_001261833.2(JRKL):​c.403A>T​(p.Ile135Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. I135V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: JRKL NM_001261833.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.01
• Publications: 1 publications found

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

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	c.403A>T	p.Ile135Phe	missense_variant	Exon 2 of 2	ENST00000332349.5	NP_001248762.1
JRKL	NM_003772.4	c.403A>T	p.Ile135Phe	missense_variant	Exon 1 of 1		NP_003763.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JRKL	ENST00000332349.5	c.403A>T	p.Ile135Phe	missense_variant	Exon 2 of 2	2	NM_001261833.2	ENSP00000333350.4
JRKL	ENST00000546177.1	n.85+979A>T		intron_variant	Intron 1 of 2	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.61	D
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.0
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.47
MutPred		0.72		Loss of methylation at K130 (P = 0.1181);
MVP		0.57
ClinPred		0.95	D
GERP RS		4.6
Varity_R		0.42
gMVP		0.71
Mutation Taster		=64/36	polymorphism

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: rs1378523836; hg19: chr11-96124216;