5-147661191-T-G

Position:

• chr5-147661191-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JAKMIP2	NM_001270941.2	c.384A>C	p.Lys128Asn	missense_variant	3/22	ENST00000616793.5
JAKMIP2-AS1	NR_038902.1	n.1102T>G		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAKMIP2	ENST00000616793.5	c.384A>C	p.Lys128Asn	missense_variant	3/22	5	NM_001270941.2	P1
JAKMIP2-AS1	ENST00000686563.1	n.508-5863T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2023

The c.384A>C (p.K128N) alteration is located in exon 3 (coding exon 2) of the JAKMIP2 gene. This alteration results from a A to C substitution at nucleotide position 384, causing the lysine (K) at amino acid position 128 to be replaced by an asparagine (N). 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	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;D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.34	T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.4	M;M;M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.2	.;D;D;D
REVEL	Benign	0.12
Sift	Uncertain	0.0030	.;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		0.73	P;.;P;.
Vest4		0.72
MutPred		0.28		Loss of ubiquitination at K128 (P = 0.0118);Loss of ubiquitination at K128 (P = 0.0118);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-147040754;