rs199810705

Variant names:

• chr5-147648469-C-A
• rs199810705
• NM_001270941.2:c.843G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001270941.2(JAKMIP2):​c.843G>T​(p.Leu281Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00007 in 1,570,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000074 (0 hom.)
• Consequence: JAKMIP2 NM_001270941.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17295304).
• BS2: High AC in GnomAd4 at 5 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.843G>T	p.Leu281Phe	missense	Exon 5 of 22	NP_001257870.1	Q96AA8-3
	JAKMIP2	NM_014790.5		c.843G>T	p.Leu281Phe	missense	Exon 5 of 21	NP_055605.2
	JAKMIP2	NM_001270934.2		c.843G>T	p.Leu281Phe	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.843G>T	p.Leu281Phe	missense	Exon 5 of 22	ENSP00000479248.1	Q96AA8-3
	JAKMIP2	ENST00000265272.9	TSL:1	c.843G>T	p.Leu281Phe	missense	Exon 5 of 21	ENSP00000265272.5	Q96AA8-1
	JAKMIP2	ENST00000507386.5	TSL:1	c.843G>T	p.Leu281Phe	missense	Exon 5 of 21	ENSP00000421398.1	Q96AA8-2

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152128 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000644 AC: 16 AN: 248480 AF XY: 0.0000671

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000142

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000740 AC: 105 AN: 1418494 Hom.: 0 Cov.: 24 AF XY: 0.0000847 AC XY: 60 AN XY: 708258

African (AFR) AF: 0.00 AC: 0 AN: 32490

American (AMR) AF: 0.00 AC: 0 AN: 44284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25806

East Asian (EAS) AF: 0.00 AC: 0 AN: 39364

South Asian (SAS) AF: 0.00 AC: 0 AN: 84522

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52496

Middle Eastern (MID) AF: 0.00141 AC: 8 AN: 5664

European-Non Finnish (NFE) AF: 0.0000819 AC: 88 AN: 1074974

Other (OTH) AF: 0.000136 AC: 8 AN: 58894

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152128 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74310

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.0000655 AC: 1 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68030

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.0000993 Hom.: 0

Bravo AF: 0.0000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000412 AC: 5

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	0.095
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.079	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.4
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.085
Sift	Benign	0.12	T
Sift4G	Benign	0.14	T
Polyphen		0.94	P
Vest4		0.35
MutPred		0.13		Loss of MoRF binding (P = 0.1235)
MVP		0.27
MPC		1.1
ClinPred		0.23	T
GERP RS		2.8
Varity_R		0.097
gMVP		0.26
Mutation Taster		=96/4	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: rs199810705; hg19: chr5-147028032;