10-132117193-G-A

Variant names:

• chr10-132117193-G-A
• rs1400030806
• NM_001323087.2:c.252G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PVS1_Supporting PM2

The NM_001392061.1(JAKMIP3):​c.3G>A​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,614 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: JAKMIP3 NM_001392061.1 start_lost
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.47
• Publications: 0 publications found

Genes affected

JAKMIP3 (HGNC:23523): (Janus kinase and microtubule interacting protein 3) Predicted to enable kinase binding activity and microtubule binding activity. Predicted to be located in Golgi apparatus. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 71 codons. Genomic position: 132117401. Lost 0.092 part of the original CDS.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001392061.1. 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
	JAKMIP3	NM_001323087.2	MANE Select	c.252G>A	p.Met84Ile	missense	Exon 3 of 24	NP_001310016.1	A0A590UJH1
	JAKMIP3	NM_001392061.1		c.3G>A	p.Met1?	start_lost	Exon 2 of 23	NP_001378990.1	A0A590UK11
	JAKMIP3	NM_001392062.1		c.3G>A	p.Met1?	start_lost	Exon 2 of 24	NP_001378991.1	A0A590UK11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAKMIP3	ENST00000684848.1	MANE Select	c.252G>A	p.Met84Ile	missense	Exon 3 of 24	ENSP00000508932.1	A0A590UJH1
	JAKMIP3	ENST00000658847.1		c.3G>A	p.Met1?	start_lost	Exon 2 of 24	ENSP00000499348.1	A0A590UK11
	JAKMIP3	ENST00000661339.1		c.3G>A	p.Met1?	start_lost	Exon 2 of 23	ENSP00000499650.1	A0A590UK11

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249230 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461614 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727098

⚠️ 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: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111868

Other (OTH) AF: 0.00 AC: 0 AN: 60372

⚠️ 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

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	0.31
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.049	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.5
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.061
Sift	Benign	0.41	T
Sift4G	Benign	0.21	T
Polyphen		0.89	P
Vest4		0.42
MutPred		0.12		Gain of methylation at K85 (P = 0.0359)
MVP		0.28
MPC		0.35
ClinPred		0.60	D
GERP RS		3.6
PromoterAI		0.040	Neutral
Varity_R		0.15
gMVP		0.51
Mutation Taster		=97/3	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: rs1400030806; hg19: chr10-133930697;