chr11-96391583-G-C

Variant names:

• chr11-96391583-G-C
• NM_001261833.2:c.934G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001261833.2(JRKL):​c.934G>C​(p.Ala312Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 3.73
• Publications: 0 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.782

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JRKL	NM_001261833.2	c.934G>C	p.Ala312Pro	missense_variant	Exon 2 of 2	ENST00000332349.5	NP_001248762.1
JRKL	NM_003772.4	c.934G>C	p.Ala312Pro	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.934G>C	p.Ala312Pro	missense_variant	Exon 2 of 2	2	NM_001261833.2	ENSP00000333350.4
JRKL	ENST00000546177.1	n.85+1510G>C		intron_variant	Intron 1 of 2	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

Jan 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.934G>C (p.A312P) alteration is located in exon 1 (coding exon 1) of the JRKL gene. This alteration results from a G to C substitution at nucleotide position 934, causing the alanine (A) at amino acid position 312 to be replaced by a proline (P). 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	0.60
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0067	T
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.7
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.20
Sift	Benign	0.041	D
Sift4G	Uncertain	0.037	D
Polyphen		0.77	P
Vest4		0.59
MutPred		0.76		Loss of sheet (P = 0.0357);
MVP		0.66
ClinPred		0.89	D
GERP RS		4.6
Varity_R		0.66
gMVP		0.90
Mutation Taster		=53/47	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

hg19: chr11-96124747;