Variant 4-6056726-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001099433.2(JAKMIP1):c.1678A>G(p.Ile560Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (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: 0.786

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:

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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=0.12512639).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
JAKMIP1	NM_001099433.2 linkuse as main transcript	c.1678A>G	p.Ile560Val	missense_variant	12/21	ENST00000409021.9
JAKMIP1	NM_001306133.2 linkuse as main transcript	c.1678A>G	p.Ile560Val	missense_variant	12/13
JAKMIP1	NM_144720.4 linkuse as main transcript	c.1678A>G	p.Ile560Val	missense_variant	12/13
JAKMIP1	NM_001306134.2 linkuse as main transcript	c.1183A>G	p.Ile395Val	missense_variant	11/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAKMIP1	ENST00000409021.9 linkuse as main transcript	c.1678A>G	p.Ile560Val	missense_variant	12/21	1	NM_001099433.2	P1	Q96N16-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461392

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727048

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 09, 2022

The c.1678A>G (p.I560V) alteration is located in exon 12 (coding exon 11) of the JAKMIP1 gene. This alteration results from a A to G substitution at nucleotide position 1678, causing the isoleucine (I) at amino acid position 560 to be replaced by a valine (V). 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

0.13

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.026

T;.;.;T;T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.81

T;T;T;.;T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.13

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

.;L;.;L;L;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.42

.;N;N;N;N;N

REVEL

Benign

0.032

Sift

Benign

0.090

.;T;T;T;T;T

Sift4G

Benign

0.38

.;T;T;T;T;T

Polyphen

0.048, 0.0010, 0.053

.;B;B;B;B;.

Vest4

0.12, 0.12, 0.12, 0.14

MutPred

0.18

.;Gain of ubiquitination at K556 (P = 0.0843);.;Gain of ubiquitination at K556 (P = 0.0843);Gain of ubiquitination at K556 (P = 0.0843);.;

MVP

0.38

MPC

0.55

ClinPred

0.10

GERP RS

3.8

Varity_R

0.046

gMVP

0.056

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over