dbSNP rs2001813: JAKMIP3:c.136-6064C>A (chr10-132111013-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is The variant received -2 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Strong

The NM_001323087.2(JAKMIP3):c.136-6064C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.00000657 (AC=1) in the gnomAD database across 152,160 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.0000654. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Consequence

JAKMIP3
NM_001323087.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.329

Publications

1 publications found

Variant links:

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]

JAKMIP3 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001323087.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 points.

PM2

Very rare in gnomAD for AR/unknown gene (popmax AF < threshold/10) — PM2; GnomAD popmax AF = 0.0000654 — very rare for unknown gene (threshold 0.001) — PM2 moderate.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001323087.2. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
JAKMIP3	NM_001323087.2	MANE Select	c.136-6064C>A	intron	N/A	NP_001310016.1	A0A590UJH1
JAKMIP3	NM_001323086.2		c.136-6064C>A	intron	N/A	NP_001310015.1	A0A590UIU4
JAKMIP3	NM_001392039.1		c.136-6064C>A	intron	N/A	NP_001378968.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
JAKMIP3	ENST00000684848.1	MANE Select	c.136-6064C>A	intron	N/A	ENSP00000508932.1	A0A590UJH1
JAKMIP3	ENST00000666210.1		c.136-6064C>A	intron	N/A	ENSP00000499222.1	A0A590UIU4
JAKMIP3	ENST00000657785.1		c.136-6064C>A	intron	N/A	ENSP00000499291.1	A0A590UJH1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41414

American (AMR)

AF:

0.0000654

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

214

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.2

(source)

DANN

Benign

0.65

PhyloP100

-0.33

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over