Genetic Variant JAKMIP3:p.Ala23Glu (chr10-132104876-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001323087.2(JAKMIP3):c.68C>A(p.Ala23Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,418,738 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A23V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

JAKMIP3
NM_001323087.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.37

Publications

1 publications found

Variant links:

Genes affected

JAKMIP3 (HGNC:23523): (Janus kinase and microtubule interacting protein 3) Predicted to enable kinase binding activity and microtubule binding activity. Predicted to be located in Golgi apparatus. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

JAKMIP3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323087.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
JAKMIP3	NM_001323087.2	MANE Select	c.68C>A	p.Ala23Glu	missense	Exon 2 of 24	NP_001310016.1	A0A590UJH1
JAKMIP3	NM_001323086.2		c.68C>A	p.Ala23Glu	missense	Exon 2 of 24	NP_001310015.1	A0A590UIU4
JAKMIP3	NM_001392039.1		c.68C>A	p.Ala23Glu	missense	Exon 2 of 25	NP_001378968.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
JAKMIP3	ENST00000684848.1	MANE Select	c.68C>A	p.Ala23Glu	missense	Exon 2 of 24	ENSP00000508932.1	A0A590UJH1
JAKMIP3	ENST00000666210.1		c.68C>A	p.Ala23Glu	missense	Exon 2 of 24	ENSP00000499222.1	A0A590UIU4
JAKMIP3	ENST00000657785.1		c.68C>A	p.Ala23Glu	missense	Exon 2 of 24	ENSP00000499291.1	A0A590UJH1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000542

AC:

AN:

184398

AF XY:

0.0000101

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000128

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1418738

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

701640

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32334

American (AMR)

AF:

0.00

AC:

AN:

38464

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25368

East Asian (EAS)

AF:

0.00

AC:

AN:

36946

South Asian (SAS)

AF:

0.00

AC:

AN:

80354

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49826

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.00000183

AC:

AN:

1090894

Other (OTH)

AF:

0.00

AC:

AN:

58846

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000838

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

0.0044

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.61

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

7.4

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.22

Sift

Benign

0.15

Sift4G

Benign

0.096

Polyphen

0.94

Vest4

0.76

MutPred

0.14

Loss of MoRF binding (P = 0.1023)

MVP

0.53

MPC

0.95

ClinPred

0.96

GERP RS

2.9

PromoterAI

0.041

Neutral

(source)

Varity_R

0.39

gMVP

0.97

Mutation Taster

=80/20

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over