Variant 4-6081697-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001099433.2(JAKMIP1):c.1013G>A(p.Arg338Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

JAKMIP1
NM_001099433.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.32

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31945062).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
JAKMIP1	NM_001099433.2 linkuse as main transcript	c.1013G>A	p.Arg338Gln	missense_variant	6/21	ENST00000409021.9
JAKMIP1	NM_001306133.2 linkuse as main transcript	c.1013G>A	p.Arg338Gln	missense_variant	6/13
JAKMIP1	NM_144720.4 linkuse as main transcript	c.1013G>A	p.Arg338Gln	missense_variant	6/13
JAKMIP1	NM_001306134.2 linkuse as main transcript	c.518G>A	p.Arg173Gln	missense_variant	5/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAKMIP1	ENST00000409021.9 linkuse as main transcript	c.1013G>A	p.Arg338Gln	missense_variant	6/21	1	NM_001099433.2	P1	Q96N16-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152168

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:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251466

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727238

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:

0.0000153

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74346

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:

0.0000941

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2023

The c.1013G>A (p.R338Q) alteration is located in exon 6 (coding exon 5) of the JAKMIP1 gene. This alteration results from a G to A substitution at nucleotide position 1013, causing the arginine (R) at amino acid position 338 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

0.25

BayesDel_addAF

Uncertain

0.077

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.30

.;.;T;T;.

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.92

LIST_S2

Pathogenic

0.97

D;D;.;D;D

M_CAP

Benign

0.034

MetaRNN

Benign

0.32

T;T;T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.2

M;.;M;M;.

MutationTaster

Benign

0.83

D;D;D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.6

D;N;D;D;D

REVEL

Benign

0.18

Sift

Benign

0.16

T;T;T;T;T

Sift4G

Benign

0.25

T;T;T;T;T

Polyphen

1.0

D;D;D;D;.

Vest4

0.46

MutPred

0.25

Gain of ubiquitination at K342 (P = 0.0292);.;Gain of ubiquitination at K342 (P = 0.0292);Gain of ubiquitination at K342 (P = 0.0292);.;

MVP

0.55

MPC

1.8

ClinPred

0.97

GERP RS

4.4

Varity_R

0.19

gMVP

0.44

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