NM_001323087.2:c.272G>C

Variant names:

• chr10-132117213-G-C
• rs753880520
• NM_001323087.2:c.272G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001323087.2(JAKMIP3):​c.272G>C​(p.Arg91Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R91H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: JAKMIP3 NM_001323087.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.58
• 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.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.816

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.272G>C	p.Arg91Pro	missense	Exon 3 of 24	NP_001310016.1	A0A590UJH1
	JAKMIP3	NM_001323086.2		c.272G>C	p.Arg91Pro	missense	Exon 3 of 24	NP_001310015.1	A0A590UIU4
	JAKMIP3	NM_001392039.1		c.272G>C	p.Arg91Pro	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.272G>C	p.Arg91Pro	missense	Exon 3 of 24	ENSP00000508932.1	A0A590UJH1
	JAKMIP3	ENST00000666210.1		c.272G>C	p.Arg91Pro	missense	Exon 3 of 24	ENSP00000499222.1	A0A590UIU4
	JAKMIP3	ENST00000657785.1		c.272G>C	p.Arg91Pro	missense	Exon 3 of 24	ENSP00000499291.1	A0A590UJH1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461648 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727104

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: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

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

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111866

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.020	T
MetaRNN	Pathogenic	0.82	D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		9.6
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.96
MutPred		0.22		Loss of MoRF binding (P = 0.0618)
MVP		0.78
MPC		1.1
ClinPred		1.0	D
GERP RS		4.5
PromoterAI		-0.014	Neutral
Varity_R		0.93
gMVP		0.95
Mutation Taster		=44/56	disease causing

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: rs753880520; hg19: chr10-133930717;