4-6054144-T-C

Position:

chr4-6054144-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001099433.2(JAKMIP1):c.1712A>G(p.Tyr571Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

JAKMIP1
NM_001099433.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.61

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:

JAKMIP1 (HGNC:):

JAKMIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09946033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAKMIP1	NM_001099433.2 linkuse as main transcript	c.1712A>G	p.Tyr571Cys	missense_variant	13/21	ENST00000409021.9	NP_001092903.1	Q96N16-2
JAKMIP1	NM_001306133.2 linkuse as main transcript	c.1712A>G	p.Tyr571Cys	missense_variant	13/13		NP_001293062.1	Q96N16-1B3KWB6
JAKMIP1	NM_144720.4 linkuse as main transcript	c.1712A>G	p.Tyr571Cys	missense_variant	13/13		NP_653321.1	Q96N16-1
JAKMIP1	NM_001306134.2 linkuse as main transcript	c.1217A>G	p.Tyr406Cys	missense_variant	12/12		NP_001293063.1	Q96N16-7B3KWB6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAKMIP1	ENST00000409021.9 linkuse as main transcript	c.1712A>G	p.Tyr571Cys	missense_variant	13/21	1	NM_001099433.2	ENSP00000386711.3		Q96N16-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251354

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135842

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727222

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000378

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

Aug 14, 2024

The c.1712A>G (p.Y571C) alteration is located in exon 13 (coding exon 12) of the JAKMIP1 gene. This alteration results from a A to G substitution at nucleotide position 1712, causing the tyrosine (Y) at amino acid position 571 to be replaced by a cysteine (C). 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

0.075

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.033

T;.;.;T;T;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.091

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.83

T;T;T;.;T;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.099

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.14

.;N;.;N;N;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.9

.;N;N;N;N;N

REVEL

Benign

0.039

Sift

Benign

0.17

.;T;T;T;T;T

Sift4G

Benign

0.20

.;T;T;T;T;T

Polyphen

0.0040, 0.0020

.;B;B;B;B;.

Vest4

0.17, 0.25, 0.17, 0.17

MutPred

0.20

.;Loss of catalytic residue at I570 (P = 0.0777);.;Loss of catalytic residue at I570 (P = 0.0777);Loss of catalytic residue at I570 (P = 0.0777);.;

MVP

0.082

MPC

0.82

ClinPred

0.29

GERP RS

4.3

Varity_R

0.10

gMVP

0.22

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