Variant 5-147629734-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001270941.2(JAKMIP2):c.1888C>T(p.Pro630Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,459,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

JAKMIP2
NM_001270941.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.54

Variant links:

Genes affected

JAKMIP2 (HGNC:29067): (janus kinase and microtubule interacting protein 2) The protein encoded by this gene is reported to be a component of the Golgi matrix. It may act as a golgin protein by negatively regulating transit of secretory cargo and by acting as a structural scaffold of the Golgi. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

JAKMIP2 links:

JAKMIP2-AS1 (HGNC:):

JAKMIP2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34112614).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAKMIP2	NM_001270941.2 linkuse as main transcript	c.1888C>T	p.Pro630Ser	missense_variant	15/22	ENST00000616793.5	NP_001257870.1	Q96AA8-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAKMIP2	ENST00000616793.5 linkuse as main transcript	c.1888C>T	p.Pro630Ser	missense_variant	15/22	5	NM_001270941.2	ENSP00000479248.1		Q96AA8-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000360

AC:

AN:

250000

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135126

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000436

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1459870

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000330

AC:

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

Oct 16, 2023

The c.1888C>T (p.P630S) alteration is located in exon 15 (coding exon 14) of the JAKMIP2 gene. This alteration results from a C to T substitution at nucleotide position 1888, causing the proline (P) at amino acid position 630 to be replaced by a serine (S). 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

0.30

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.050

.;.;T;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

T;T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.34

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.95

L;.;L;.

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.2

.;N;N;N

REVEL

Uncertain

0.35

Sift

Benign

0.71

.;T;T;T

Sift4G

Benign

0.29

T;T;T;T

Polyphen

1.0

D;.;D;.

Vest4

0.62

MutPred

0.24

Loss of stability (P = 0.076);.;Loss of stability (P = 0.076);.;

MVP

0.38

MPC

2.5

ClinPred

0.20

GERP RS

5.8

Varity_R

0.16

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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