17-75267582-G-A

Variant summary

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

The NM_001370592.1(MIF4GD):​c.397C>T​(p.Leu133Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MIF4GD
NM_001370592.1 missense

Scores

4
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.51
Variant links:
Genes affected
MIF4GD (HGNC:24030): (MIF4G domain containing) This gene encodes a protein which interacts with the N-terminus of the stem-loop binding protein (SLBP) and the 3' end of histone mRNA. This interaction facilitates the activation of histone mRNA translation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
MIF4GDNM_001370592.1 linkuse as main transcriptc.397C>T p.Leu133Phe missense_variant 5/6 ENST00000325102.13 NP_001357521.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MIF4GDENST00000325102.13 linkuse as main transcriptc.397C>T p.Leu133Phe missense_variant 5/62 NM_001370592.1 ENSP00000321625 P1A9UHW6-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251446
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135904
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461872
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 30, 2023The c.520C>T (p.L174F) alteration is located in exon 6 (coding exon 5) of the MIF4GD gene. This alteration results from a C to T substitution at nucleotide position 520, causing the leucine (L) at amino acid position 174 to be replaced by a phenylalanine (F). 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
0.28
BayesDel_addAF
Benign
-0.0038
T
BayesDel_noAF
Uncertain
-0.060
CADD
Pathogenic
28
DANN
Uncertain
0.98
DEOGEN2
Benign
0.13
T;T;.;.;.;.;.;.;T;.
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.90
.;D;D;.;D;D;D;D;D;D
M_CAP
Benign
0.013
T
MetaRNN
Uncertain
0.61
D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.68
T
MutationAssessor
Uncertain
2.6
M;M;.;.;.;.;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Uncertain
0.62
T
PROVEAN
Uncertain
-2.8
D;.;D;.;.;.;.;.;.;.
REVEL
Uncertain
0.30
Sift
Pathogenic
0.0
D;.;D;.;.;.;.;.;.;.
Sift4G
Uncertain
0.015
D;D;D;D;D;D;.;D;.;.
Polyphen
1.0
D;D;D;.;.;.;.;.;.;.
Vest4
0.88
MutPred
0.61
Loss of catalytic residue at L133 (P = 0.0579);Loss of catalytic residue at L133 (P = 0.0579);.;.;.;.;.;Loss of catalytic residue at L133 (P = 0.0579);Loss of catalytic residue at L133 (P = 0.0579);.;
MVP
0.52
MPC
0.87
ClinPred
0.86
D
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.70
gMVP
0.62

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs780556531; hg19: chr17-73263663; API