10-132117492-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001323087.2(JAKMIP3):​c.551C>A​(p.Ala184Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,354 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

JAKMIP3
NM_001323087.2 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.321
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
JAKMIP3NM_001323087.2 linkc.551C>A p.Ala184Glu missense_variant Exon 3 of 24 ENST00000684848.1 NP_001310016.1 A0A590UJH1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
JAKMIP3ENST00000684848.1 linkc.551C>A p.Ala184Glu missense_variant Exon 3 of 24 NM_001323087.2 ENSP00000508932.1 A0A590UJH1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152150
Hom.:
0
Cov.:
32
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000410
AC:
1
AN:
243960
Hom.:
0
AF XY:
0.00000753
AC XY:
1
AN XY:
132760
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:
0.00000910
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1460204
Hom.:
0
Cov.:
33
AF XY:
0.00000551
AC XY:
4
AN XY:
726308
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:
0.00000270
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152150
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74318
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:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.00000827
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.551C>A (p.A184E) alteration is located in exon 2 (coding exon 2) of the JAKMIP3 gene. This alteration results from a C to A substitution at nucleotide position 551, causing the alanine (A) at amino acid position 184 to be replaced by a glutamic acid (E). 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
Uncertain
0.54
BayesDel_addAF
Benign
-0.087
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.26
T
Eigen
Uncertain
0.20
Eigen_PC
Benign
0.11
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.81
T
M_CAP
Benign
0.0072
T
MetaRNN
Uncertain
0.50
D
MetaSVM
Benign
-0.95
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Uncertain
0.64
T
PROVEAN
Uncertain
-2.9
D
REVEL
Benign
0.16
Sift
Benign
0.12
T
Sift4G
Benign
0.85
T
Polyphen
1.0
D
Vest4
0.63
MutPred
0.26
Gain of disorder (P = 0.0341);
MVP
0.36
MPC
0.99
ClinPred
0.94
D
GERP RS
4.7
Varity_R
0.54
gMVP
0.39

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.

Other links and lift over

dbSNP: rs778281162; hg19: chr10-133930996; API