chr5-147648404-G-A

Variant names:

• chr5-147648404-G-A
• rs752022916
• NM_001270941.2:c.908C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001270941.2(JAKMIP2):​c.908C>T​(p.Thr303Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000367 in 1,607,670 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: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: JAKMIP2 NM_001270941.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.21
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05343002).
• BS2: High AC in GnomAdExome4 at 57 AD gene.

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.908C>T	p.Thr303Ile	missense	Exon 5 of 22	NP_001257870.1	Q96AA8-3
	JAKMIP2	NM_014790.5		c.908C>T	p.Thr303Ile	missense	Exon 5 of 21	NP_055605.2
	JAKMIP2	NM_001270934.2		c.908C>T	p.Thr303Ile	missense	Exon 5 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.908C>T	p.Thr303Ile	missense	Exon 5 of 22	ENSP00000479248.1	Q96AA8-3
	JAKMIP2	ENST00000265272.9	TSL:1	c.908C>T	p.Thr303Ile	missense	Exon 5 of 21	ENSP00000265272.5	Q96AA8-1
	JAKMIP2	ENST00000507386.5	TSL:1	c.908C>T	p.Thr303Ile	missense	Exon 5 of 21	ENSP00000421398.1	Q96AA8-2

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151996 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000203 AC: 51 AN: 250950 AF XY: 0.000170

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00125

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.0000392 AC: 57 AN: 1455674 Hom.: 0 Cov.: 28 AF XY: 0.0000359 AC XY: 26 AN XY: 724608

African (AFR) AF: 0.00 AC: 0 AN: 33332

American (AMR) AF: 0.00119 AC: 53 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39586

South Asian (SAS) AF: 0.00 AC: 0 AN: 86052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106908

Other (OTH) AF: 0.0000665 AC: 4 AN: 60154

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151996 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74252

African (AFR) AF: 0.00 AC: 0 AN: 41392

American (AMR) AF: 0.000131 AC: 2 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000444 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.000280 AC: 34

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	0.23
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.053	T
MetaSVM	Uncertain	0.21	D
MutationAssessor	Benign	1.6	L
PhyloP100		9.2
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.011	D
Polyphen		0.95	P
Vest4		0.49
MutPred		0.13		Loss of phosphorylation at T303 (P = 0.0418)
MVP		0.28
MPC		1.1
ClinPred		0.23	T
GERP RS		5.3
Varity_R		0.41
gMVP		0.40
Mutation Taster		=61/39	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: rs752022916; hg19: chr5-147027967; COSMIC: COSV108086862; COSMIC: COSV108086862;