chr11-96390837-G-C

Variant names:

• chr11-96390837-G-C
• rs890386780
• NM_001261833.2:c.188G>C

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.188G>C​(p.Ser63Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. S63N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: JRKL NM_001261833.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.08
• 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=0.117978424).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JRKL	NM_001261833.2	c.188G>C	p.Ser63Thr	missense_variant	Exon 2 of 2	ENST00000332349.5	NP_001248762.1
JRKL	NM_003772.4	c.188G>C	p.Ser63Thr	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.188G>C	p.Ser63Thr	missense_variant	Exon 2 of 2	2	NM_001261833.2	ENSP00000333350.4
JRKL	ENST00000546177.1	n.85+764G>C		intron_variant	Intron 1 of 2	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461098 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726864

African (AFR) AF: 0.00 AC: 0 AN: 33366

American (AMR) AF: 0.00 AC: 0 AN: 44510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111838

Other (OTH) AF: 0.00 AC: 0 AN: 60338

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Benign	0.89
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.077
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.1
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.044
Sift	Benign	0.063	T
Sift4G	Benign	0.72	T
Polyphen		0.056	B
Vest4		0.14
MutPred		0.19		Loss of phosphorylation at S63 (P = 0.0621);
MVP		0.38
ClinPred		0.66	D
GERP RS		3.7
Varity_R		0.14
gMVP		0.52
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs890386780; hg19: chr11-96124001;