10-132117459-C-T

Variant names:

• chr10-132117459-C-T
• rs371280434
• NM_001323087.2:c.518C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001323087.2(JAKMIP3):​c.518C>T​(p.Thr173Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000171 in 1,613,800 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (1 hom.)
• Consequence: JAKMIP3 NM_001323087.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.572
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24880618).

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.518C>T	p.Thr173Met	missense	Exon 3 of 24	NP_001310016.1	A0A590UJH1
	JAKMIP3	NM_001323086.2		c.518C>T	p.Thr173Met	missense	Exon 3 of 24	NP_001310015.1	A0A590UIU4
	JAKMIP3	NM_001392039.1		c.518C>T	p.Thr173Met	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.518C>T	p.Thr173Met	missense	Exon 3 of 24	ENSP00000508932.1	A0A590UJH1
	JAKMIP3	ENST00000666210.1		c.518C>T	p.Thr173Met	missense	Exon 3 of 24	ENSP00000499222.1	A0A590UIU4
	JAKMIP3	ENST00000657785.1		c.518C>T	p.Thr173Met	missense	Exon 3 of 24	ENSP00000499291.1	A0A590UJH1

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000724 AC: 18 AN: 248772 AF XY: 0.0000889

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

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: 0.000181 AC: 264 AN: 1461606 Hom.: 1 Cov.: 33 AF XY: 0.000176 AC XY: 128 AN XY: 727080

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86248

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.000220 AC: 245 AN: 1111858

Other (OTH) AF: 0.000199 AC: 12 AN: 60374

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7 AN XY: 74344

African (AFR) AF: 0.0000241 AC: 1 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

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: 0.000162 AC: 11 AN: 68036

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

Alfa AF: 0.000147 Hom.: 0

Bravo AF: 0.0000793

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000117 AC: 1

ExAC AF: 0.000107 AC: 13

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	0.088
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.54
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.081	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Benign	0.51	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.57
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.077
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.43
MVP		0.25
MPC		0.81
ClinPred		0.35	T
GERP RS		4.7
PromoterAI		-0.052	Neutral
Varity_R		0.21
gMVP		0.30
Mutation Taster		=82/18	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: rs371280434; hg19: chr10-133930963; COSMIC: COSV53830244;