Variant chr4-6062401-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001099433.2(JAKMIP1):c.1471C>A(p.Leu491Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,613,712 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

JAKMIP1
NM_001099433.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.71

Variant links:

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]

JAKMIP1 links:

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

C4orf50 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
JAKMIP1	NM_001099433.2 linkuse as main transcript	c.1471C>A	p.Leu491Met	missense_variant	10/21	ENST00000409021.9
JAKMIP1	NM_001306133.2 linkuse as main transcript	c.1471C>A	p.Leu491Met	missense_variant	10/13
JAKMIP1	NM_144720.4 linkuse as main transcript	c.1471C>A	p.Leu491Met	missense_variant	10/13
JAKMIP1	NM_001306134.2 linkuse as main transcript	c.976C>A	p.Leu326Met	missense_variant	9/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAKMIP1	ENST00000409021.9 linkuse as main transcript	c.1471C>A	p.Leu491Met	missense_variant	10/21	1	NM_001099433.2	P1	Q96N16-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461452

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727028

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Feb 12, 2021

PP3, PM2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;.;.;T;T;.

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

1.0

D;D;D;.;D;D

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.53

D;D;D;D;D;D

MetaSVM

Uncertain

-0.083

MutationAssessor

Uncertain

2.2

.;M;.;M;M;.

MutationTaster

Benign

0.92

D;D;D;D;D

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.6

.;N;N;N;N;N

REVEL

Benign

0.23

Sift

Pathogenic

0.0

.;D;D;D;D;D

Sift4G

Uncertain

0.023

.;D;D;D;D;D

Polyphen

1.0

.;D;D;D;D;.

Vest4

0.86, 0.77, 0.86, 0.86

MVP

0.84

MPC

1.6

ClinPred

0.94

GERP RS

4.7

Varity_R

0.58

gMVP

0.37

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over