4-6064920-G-A

Position:

• chr4-6064920-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000409021.9(JAKMIP1):​c.1391C>T​(p.Thr464Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: JAKMIP1 ENST00000409021.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 7.27

Genes affected

JAKMIP1 (HGNC:26460): (janus kinase and microtubule interacting protein 1) Enables GABA receptor binding activity and RNA binding activity. Involved in cognition. Is extrinsic component of membrane. Part of ribonucleoprotein complex. [provided by Alliance of Genome Resources, Apr 2022]

C4orf50 (HGNC:33766): (chromosome 4 open reading frame 50)

JAKMIP1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAKMIP1	NM_001099433.2	c.1391C>T	p.Thr464Ile	missense_variant	9/21	ENST00000409021.9	NP_001092903.1
JAKMIP1	NM_001306133.2	c.1391C>T	p.Thr464Ile	missense_variant	9/13		NP_001293062.1
JAKMIP1	NM_144720.4	c.1391C>T	p.Thr464Ile	missense_variant	9/13		NP_653321.1
JAKMIP1	NM_001306134.2	c.896C>T	p.Thr299Ile	missense_variant	8/12		NP_001293063.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAKMIP1	ENST00000409021.9	c.1391C>T	p.Thr464Ile	missense_variant	9/21	1	NM_001099433.2	ENSP00000386711.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.1391C>T (p.T464I) alteration is located in exon 9 (coding exon 8) of the JAKMIP1 gene. This alteration results from a C to T substitution at nucleotide position 1391, causing the threonine (T) at amino acid position 464 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.18	T;.;.;T;T;.
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D;D;D;.;D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.51	D;D;D;D;D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	2.0	.;M;.;M;M;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-3.6	.;D;D;D;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	.;D;D;D;D;D
Sift4G	Benign	0.10	.;T;T;T;T;T
Polyphen		0.93, 1.0	.;P;P;D;D;.
Vest4		0.76, 0.73, 0.69, 0.72
MutPred		0.17		.;Loss of phosphorylation at T464 (P = 0.0193);.;Loss of phosphorylation at T464 (P = 0.0193);Loss of phosphorylation at T464 (P = 0.0193);.;
MVP		0.41
MPC		1.7
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.48
gMVP		0.27

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: rs995849470; hg19: chr4-6066647;