10-132104867-C-T

Variant names:

• chr10-132104867-C-T
• rs756701841
• NM_001323087.2:c.59C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001323087.2(JAKMIP3):​c.59C>T​(p.Ala20Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000896 in 1,563,168 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. A20T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000085 (0 hom.)
• Consequence: JAKMIP3 NM_001323087.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.53
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23021811).

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.59C>T	p.Ala20Val	missense	Exon 2 of 24	NP_001310016.1	A0A590UJH1
	JAKMIP3	NM_001323086.2		c.59C>T	p.Ala20Val	missense	Exon 2 of 24	NP_001310015.1	A0A590UIU4
	JAKMIP3	NM_001392039.1		c.59C>T	p.Ala20Val	missense	Exon 2 of 25	NP_001378968.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAKMIP3	ENST00000684848.1	MANE Select	c.59C>T	p.Ala20Val	missense	Exon 2 of 24	ENSP00000508932.1	A0A590UJH1
	JAKMIP3	ENST00000666210.1		c.59C>T	p.Ala20Val	missense	Exon 2 of 24	ENSP00000499222.1	A0A590UIU4
	JAKMIP3	ENST00000657785.1		c.59C>T	p.Ala20Val	missense	Exon 2 of 24	ENSP00000499291.1	A0A590UJH1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152224 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

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: 0.00000574 AC: 1 AN: 174224 AF XY: 0.0000108

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: 0.00000850 AC: 12 AN: 1410944 Hom.: 0 Cov.: 30 AF XY: 0.0000115 AC XY: 8 AN XY: 697026

African (AFR) AF: 0.0000312 AC: 1 AN: 32070

American (AMR) AF: 0.00 AC: 0 AN: 37164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25288

East Asian (EAS) AF: 0.000137 AC: 5 AN: 36504

South Asian (SAS) AF: 0.0000251 AC: 2 AN: 79826

European-Finnish (FIN) AF: 0.0000404 AC: 2 AN: 49472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000184 AC: 2 AN: 1086350

Other (OTH) AF: 0.00 AC: 0 AN: 58572

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152224 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74366

African (AFR) AF: 0.0000241 AC: 1 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000847 AC: 1

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	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		4.5
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.076
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.048	D
Polyphen		0.88	P
Vest4		0.27
MutPred		0.19		Gain of MoRF binding (P = 0.134)
MVP		0.32
MPC		0.52
ClinPred		0.80	D
GERP RS		2.9
PromoterAI		-0.0062	Neutral
Varity_R		0.17
gMVP		0.79
Mutation Taster		=90/10	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: rs756701841; hg19: chr10-133918371;