1-153974734-C-T

Position:

• chr1-153974734-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006694.4(JTB):​c.386G>A​(p.Arg129Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000178 in 1,461,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: JTB NM_006694.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.83

Genes affected

JTB (HGNC:6201): (jumping translocation breakpoint) Enables protein kinase binding activity. Involved in mitotic cytokinesis and positive regulation of protein kinase activity. Located in cytoplasm and midbody. Colocalizes with centrosome and spindle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.927

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JTB	NM_006694.4	c.386G>A	p.Arg129Gln	missense_variant	5/5	ENST00000271843.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JTB	ENST00000271843.9	c.386G>A	p.Arg129Gln	missense_variant	5/5	1	NM_006694.4	P1
JTB	ENST00000356648.5	c.299G>A	p.Arg100Gln	missense_variant	5/5	2
JTB	ENST00000368589.5	c.299G>A	p.Arg100Gln	missense_variant	4/4	2
JTB	ENST00000428469.1	c.299G>A	p.Arg100Gln	missense_variant	4/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000178 AC: 26 AN: 1461596 Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12 AN XY: 727068

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000216

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Nov 07, 2023

The c.386G>A (p.R129Q) alteration is located in exon 5 (coding exon 5) of the JTB gene. This alteration results from a G to A substitution at nucleotide position 386, causing the arginine (R) at amino acid position 129 to be replaced by a glutamine (Q). 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	0.11
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.22	T;.;.;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.93	D;.;.;D
M_CAP	Benign	0.055	D
MetaRNN	Pathogenic	0.93	D;D;D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.1	M;.;.;.
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.8	D;D;D;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0050	D;D;D;D
Sift4G	Uncertain	0.027	D;D;D;D
Polyphen		1.0	D;.;.;.
Vest4		0.66
MutPred		0.91		Loss of MoRF binding (P = 0.0274);.;.;.;
MVP		0.47
MPC		1.8
ClinPred		0.98	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.88

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

LitVar

Other links and lift over

dbSNP: rs913009595; hg19: chr1-153947210;