5-147644171-G-C

Variant names:

• chr5-147644171-G-C
• rs766979419
• NM_001270941.2:c.1111C>G

Variant summary

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

The NM_001270941.2(JAKMIP2):​c.1111C>G​(p.Leu371Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,838 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L371M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: JAKMIP2 NM_001270941.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• 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=0.372342).

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.1111C>G	p.Leu371Val	missense	Exon 7 of 22	NP_001257870.1	Q96AA8-3
	JAKMIP2	NM_014790.5		c.1111C>G	p.Leu371Val	missense	Exon 7 of 21	NP_055605.2
	JAKMIP2	NM_001270934.2		c.1111C>G	p.Leu371Val	missense	Exon 7 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.1111C>G	p.Leu371Val	missense	Exon 7 of 22	ENSP00000479248.1	Q96AA8-3
	JAKMIP2	ENST00000265272.9	TSL:1	c.1111C>G	p.Leu371Val	missense	Exon 7 of 21	ENSP00000265272.5	Q96AA8-1
	JAKMIP2	ENST00000507386.5	TSL:1	c.1111C>G	p.Leu371Val	missense	Exon 7 of 21	ENSP00000421398.1	Q96AA8-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440838 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 713040

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33162

American (AMR) AF: 0.00 AC: 0 AN: 44224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25762

East Asian (EAS) AF: 0.00 AC: 0 AN: 39136

South Asian (SAS) AF: 0.00 AC: 0 AN: 83412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 9.12e-7 AC: 1 AN: 1096912

Other (OTH) AF: 0.00 AC: 0 AN: 59478

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.058
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.6
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.23
Sift	Benign	0.057	T
Sift4G	Uncertain	0.041	D
Polyphen		0.97	D
Vest4		0.59
MutPred		0.24		Gain of methylation at K372 (P = 0.0313)
MVP		0.28
MPC		1.6
ClinPred		0.95	D
GERP RS		-1.1
Varity_R		0.083
gMVP		0.25
Mutation Taster		=91/9	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: rs766979419; hg19: chr5-147023734;