NM_001270941.2:c.384A>C

Variant names:

• chr5-147661191-T-G
• rs540737599
• NM_001270941.2:c.384A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001270941.2(JAKMIP2):​c.384A>C​(p.Lys128Asn) 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. 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: 2.79
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3373663).

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.384A>C	p.Lys128Asn	missense	Exon 3 of 22	NP_001257870.1	Q96AA8-3
	JAKMIP2	NM_014790.5		c.384A>C	p.Lys128Asn	missense	Exon 3 of 21	NP_055605.2
	JAKMIP2	NM_001270934.2		c.384A>C	p.Lys128Asn	missense	Exon 3 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.384A>C	p.Lys128Asn	missense	Exon 3 of 22	ENSP00000479248.1	Q96AA8-3
	JAKMIP2	ENST00000265272.9	TSL:1	c.384A>C	p.Lys128Asn	missense	Exon 3 of 21	ENSP00000265272.5	Q96AA8-1
	JAKMIP2	ENST00000507386.5	TSL:1	c.384A>C	p.Lys128Asn	missense	Exon 3 of 21	ENSP00000421398.1	Q96AA8-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Pathogenic	0.95
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	T
Eigen	Benign	0.056
Eigen_PC	Benign	0.049
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.8
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.12
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.73	P
Vest4		0.72
MutPred		0.28		Loss of ubiquitination at K128 (P = 0.0118)
MVP		0.20
MPC		1.5
ClinPred		0.97	D
GERP RS		3.6
Varity_R		0.61
gMVP		0.52
Mutation Taster		=46/54	disease causing

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: rs540737599; hg19: chr5-147040754;