5-147644158-T-C

Variant names:

• chr5-147644158-T-C
• rs754943679
• NM_001270941.2:c.1124A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001270941.2(JAKMIP2):​c.1124A>G​(p.Lys375Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: JAKMIP2 NM_001270941.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.21
• Publications: 0 publications found

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-AS1 (HGNC:27203): (JAKMIP2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06895274).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270941.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAKMIP2	NM_001270941.2	MANE Select	c.1124A>G	p.Lys375Arg	missense	Exon 7 of 22	NP_001257870.1	Q96AA8-3
	JAKMIP2	NM_014790.5		c.1124A>G	p.Lys375Arg	missense	Exon 7 of 21	NP_055605.2
	JAKMIP2	NM_001270934.2		c.1124A>G	p.Lys375Arg	missense	Exon 7 of 21	NP_001257863.1	Q96AA8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAKMIP2	ENST00000616793.5	TSL:5 MANE Select	c.1124A>G	p.Lys375Arg	missense	Exon 7 of 22	ENSP00000479248.1	Q96AA8-3
	JAKMIP2	ENST00000265272.9	TSL:1	c.1124A>G	p.Lys375Arg	missense	Exon 7 of 21	ENSP00000265272.5	Q96AA8-1
	JAKMIP2	ENST00000507386.5	TSL:1	c.1124A>G	p.Lys375Arg	missense	Exon 7 of 21	ENSP00000421398.1	Q96AA8-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.0053
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.2
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.076
Sift	Benign	0.20	T
Sift4G	Benign	0.87	T
Polyphen		0.0040	B
Vest4		0.14
MutPred		0.087		Loss of ubiquitination at K375 (P = 0.0244)
MVP		0.13
MPC		0.50
ClinPred		0.69	D
GERP RS		5.5
Varity_R		0.099
gMVP		0.11
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs754943679; hg19: chr5-147023721;