chr4-6062440-C-T

Position:

chr4-6062440-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001099433.2(JAKMIP1):c.1432G>A(p.Ala478Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,612,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

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

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

JAKMIP1
NM_001099433.2 missense, splice_region

Scores

Splicing: ADA: 0.01221

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.729

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.023429364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAKMIP1	NM_001099433.2 linkuse as main transcript	c.1432G>A	p.Ala478Thr	missense_variant, splice_region_variant	10/21	ENST00000409021.9	NP_001092903.1	Q96N16-2
JAKMIP1	NM_001306133.2 linkuse as main transcript	c.1432G>A	p.Ala478Thr	missense_variant, splice_region_variant	10/13		NP_001293062.1	Q96N16-1B3KWB6
JAKMIP1	NM_144720.4 linkuse as main transcript	c.1432G>A	p.Ala478Thr	missense_variant, splice_region_variant	10/13		NP_653321.1	Q96N16-1
JAKMIP1	NM_001306134.2 linkuse as main transcript	c.937G>A	p.Ala313Thr	missense_variant, splice_region_variant	9/12		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.1432G>A	p.Ala478Thr	missense_variant, splice_region_variant	10/21	1	NM_001099433.2	ENSP00000386711.3		Q96N16-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000799

AC:

AN:

250162

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135508

show subpopulations

Gnomad AFR exome

AF:

0.000125

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1459992

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

726026

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.70

CADD

Benign

7.5

DANN

Benign

0.75

DEOGEN2

Benign

0.013

T;.;.;T;T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.69

T;T;T;.;T;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.023

T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.34

.;N;.;N;N;.

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.78

.;N;N;N;N;N

REVEL

Benign

0.037

Sift

Benign

0.35

.;T;T;T;T;T

Sift4G

Benign

0.39

.;T;T;T;T;T

Polyphen

0.0

.;B;B;B;B;.

Vest4

0.13, 0.12, 0.13, 0.11

MutPred

0.20

.;Gain of glycosylation at A478 (P = 0.0306);.;Gain of glycosylation at A478 (P = 0.0306);Gain of glycosylation at A478 (P = 0.0306);.;

MVP

0.22

MPC

0.63

ClinPred

0.0081

GERP RS

-1.0

Varity_R

0.018

gMVP

0.064

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.012

dbscSNV1_RF

Benign

0.23

SpliceAI score (max)

0.020

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