11-96392063-C-A

Variant names:

• chr11-96392063-C-A
• rs1329636018
• NM_001261833.2:c.1414C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001261833.2(JRKL):​c.1414C>A​(p.Pro472Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 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. P472A) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: JRKL NM_001261833.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.60
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24747005).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001261833.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JRKL	NM_001261833.2	MANE Select	c.1414C>A	p.Pro472Thr	missense	Exon 2 of 2	NP_001248762.1	Q9Y4A0
	JRKL	NM_003772.4		c.1414C>A	p.Pro472Thr	missense	Exon 1 of 1	NP_003763.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JRKL	ENST00000332349.5	TSL:2 MANE Select	c.1414C>A	p.Pro472Thr	missense	Exon 2 of 2	ENSP00000333350.4	Q9Y4A0
	JRKL	ENST00000546177.1	TSL:1	n.85+1990C>A		intron	N/A
	JRKL	ENST00000931498.1		c.1414C>A	p.Pro472Thr	missense	Exon 2 of 2	ENSP00000601557.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152134 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152134 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74318

African (AFR) AF: 0.00 AC: 0 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.6
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.056
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.046	D
Polyphen		0.99	D
Vest4		0.27
MutPred		0.27		Gain of glycosylation at P472 (P = 0.0574)
MVP		0.53
ClinPred		0.86	D
GERP RS		3.9
Varity_R		0.12
gMVP		0.34
Mutation Taster		=74/26	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: rs1329636018; hg19: chr11-96125227;