chr22-23894805-A-C

Position:

• chr22-23894805-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002415.2(MIF):​c.142A>C​(p.Met48Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MIF NM_002415.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.02

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]

ENSG00000251357 (HGNC:):

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIF	NM_002415.2	c.142A>C	p.Met48Leu	missense_variant	2/3	ENST00000215754.8	NP_002406.1
MIF-AS1	NR_038911.1	n.1097T>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIF	ENST00000215754.8	c.142A>C	p.Met48Leu	missense_variant	2/3	1	NM_002415.2	ENSP00000215754.7
ENSG00000251357	ENST00000433835.3	c.465A>C	p.Ser155Ser	synonymous_variant	5/6	5		ENSP00000400325.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 26, 2024

The c.142A>C (p.M48L) alteration is located in exon 2 (coding exon 2) of the MIF gene. This alteration results from a A to C substitution at nucleotide position 142, causing the methionine (M) at amino acid position 48 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Uncertain	0.75	D
Eigen	Benign	-0.11
Eigen_PC	Benign	0.0032
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.26
Sift	Benign	0.060	T
Sift4G	Benign	0.099	T
Polyphen		0.055	B
Vest4		0.65
MutPred		0.72		Gain of sheet (P = 0.1451);
MVP		0.35
MPC		0.78
ClinPred		0.97	D
GERP RS		3.9
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.77
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-24236992;