dbSNP rs532485317: MIF:p.Ile65Met (chr22-23894858-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM1PP3

The NM_002415.2(MIF):c.195C>G(p.Ile65Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,554,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

MIF
NM_002415.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0420

Publications

1 publications found

Variant links:

Genes affected

MIF (HGNC:7097): (macrophage migration inhibitory factor) This gene encodes a lymphokine involved in cell-mediated immunity, immunoregulation, and inflammation. It plays a role in the regulation of macrophage function in host defense through the suppression of anti-inflammatory effects of glucocorticoids. This lymphokine and the JAB1 protein form a complex in the cytosol near the peripheral plasma membrane, which may indicate an additional role in integrin signaling pathways. [provided by RefSeq, Jul 2008]

MIF links:

ENSG00000251357 (HGNC:):

ENSG00000251357 links:

MIF-AS1 (HGNC:27669): (MIF antisense RNA 1)

MIF-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity MIF_HUMAN

PP3

MetaRNN computational evidence supports a deleterious effect, 0.758

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002415.2. 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
	MIF	NM_002415.2	MANE Select	c.195C>G	p.Ile65Met	missense	Exon 2 of 3	NP_002406.1	P14174
	MIF-AS1	NR_038911.1		n.1044G>C		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MIF	ENST00000215754.8	TSL:1 MANE Select	c.195C>G	p.Ile65Met	missense	Exon 2 of 3	ENSP00000215754.7	P14174
ENSG00000251357	ENST00000433835.3	TSL:5	c.518C>G	p.Ser173Trp	missense	Exon 5 of 6	ENSP00000400325.3	H7C1H1
MIF-AS1	ENST00000406213.1	TSL:1	n.1044G>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00174

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:

0.000113

AC:

AN:

151028

AF XY:

0.0000964

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00146

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1402366

Hom.:

Cov.:

AF XY:

0.0000144

AC XY:

AN XY:

693372

show subpopulations

African (AFR)

AF:

0.0000311

AC:

AN:

32148

American (AMR)

AF:

0.00

AC:

AN:

37154

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25254

East Asian (EAS)

AF:

0.000465

AC:

AN:

36534

South Asian (SAS)

AF:

0.00

AC:

AN:

80204

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1085674

Other (OTH)

AF:

0.0000686

AC:

AN:

58350

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

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41574

American (AMR)

AF:

0.00

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00174

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000266

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.83

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.76

MetaSVM

Benign

-0.50

MutationAssessor

Pathogenic

4.2

PhyloP100

-0.042

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.44

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.83

MutPred

0.89

Gain of disorder (P = 0.0561)

MVP

0.32

MPC

1.8

ClinPred

0.94

GERP RS

0.25

PromoterAI

0.045

Neutral

(source)

Varity_R

0.95

gMVP

0.79

Mutation Taster

=44/56

disease causing

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over