5-147644158-T-C

Position:

• chr5-147644158-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 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

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 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JAKMIP2	NM_001270941.2	c.1124A>G	p.Lys375Arg	missense_variant	7/22	ENST00000616793.5
JAKMIP2-AS1	NR_038902.1	n.364-16295T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAKMIP2	ENST00000616793.5	c.1124A>G	p.Lys375Arg	missense_variant	7/22	5	NM_001270941.2	P1
JAKMIP2-AS1	ENST00000686563.1	n.507+7753T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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

Mar 11, 2024

The c.1124A>G (p.K375R) alteration is located in exon 7 (coding exon 6) of the JAKMIP2 gene. This alteration results from a A to G substitution at nucleotide position 1124, causing the lysine (K) at amino acid position 375 to be replaced by an arginine (R). 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	0.076
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	22
DANN	Uncertain	0.99
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.0053
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.85	T;D;T;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.069	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;N;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.66	T
Sift4G	Benign	0.87	T;T;T;T
Polyphen		0.0040	B;.;B;.
Vest4		0.14
MutPred		0.087		Loss of ubiquitination at K375 (P = 0.0244);Loss of ubiquitination at K375 (P = 0.0244);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

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

Other links and lift over

dbSNP: rs754943679; hg19: chr5-147023721;