10-132117122-C-T

Variant names:

• chr10-132117122-C-T
• rs780173989
• NM_001323087.2:c.181C>T

Variant summary

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

The NM_001323087.2(JAKMIP3):​c.181C>T​(p.Arg61Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,612,734 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R61H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: JAKMIP3 NM_001323087.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.64
• Publications: 2 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36353457).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323087.2. 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
	JAKMIP3	NM_001323087.2	MANE Select	c.181C>T	p.Arg61Cys	missense	Exon 3 of 24	NP_001310016.1	A0A590UJH1
	JAKMIP3	NM_001323086.2		c.181C>T	p.Arg61Cys	missense	Exon 3 of 24	NP_001310015.1	A0A590UIU4
	JAKMIP3	NM_001392039.1		c.181C>T	p.Arg61Cys	missense	Exon 3 of 25	NP_001378968.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAKMIP3	ENST00000684848.1	MANE Select	c.181C>T	p.Arg61Cys	missense	Exon 3 of 24	ENSP00000508932.1	A0A590UJH1
	JAKMIP3	ENST00000666210.1		c.181C>T	p.Arg61Cys	missense	Exon 3 of 24	ENSP00000499222.1	A0A590UIU4
	JAKMIP3	ENST00000657785.1		c.181C>T	p.Arg61Cys	missense	Exon 3 of 24	ENSP00000499291.1	A0A590UJH1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152242 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000161 AC: 4 AN: 247810 AF XY: 0.0000297

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: 0.0000358

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1460492 Hom.: 0 Cov.: 33 AF XY: 0.0000179 AC XY: 13 AN XY: 726406

African (AFR) AF: 0.0000299 AC: 1 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111222

Other (OTH) AF: 0.00 AC: 0 AN: 60340

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152242 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74382

African (AFR) AF: 0.00 AC: 0 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.27
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.6
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.49
MutPred		0.22		Loss of MoRF binding (P = 0.0082)
MVP		0.43
MPC		1.1
ClinPred		0.94	D
GERP RS		3.5
PromoterAI		-0.0024	Neutral
Varity_R		0.54
gMVP		0.69
Mutation Taster		=81/19	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: rs780173989; hg19: chr10-133930626;