17-75267849-C-T

Variant summary

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

The NM_001370592.1(MIF4GD):​c.245G>A​(p.Arg82Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,612 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: 0.0000014 ( 0 hom. )

Consequence

MIF4GD
NM_001370592.1 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.44
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 rank MANE Protein UniProt
MIF4GDNM_001370592.1 linkc.245G>A p.Arg82Gln missense_variant Exon 4 of 6 ENST00000325102.13 NP_001357521.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MIF4GDENST00000325102.13 linkc.245G>A p.Arg82Gln missense_variant Exon 4 of 6 2 NM_001370592.1 ENSP00000321625.8 A9UHW6-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461612
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727104
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 30, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.368G>A (p.R123Q) alteration is located in exon 5 (coding exon 4) of the MIF4GD gene. This alteration results from a G to A substitution at nucleotide position 368, causing the arginine (R) at amino acid position 123 to be replaced by a glutamine (Q). 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
0.15
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.010
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.033
T;T;.;.;.;.;.;T;T;T
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.90
.;D;D;.;D;D;D;D;D;D
M_CAP
Benign
0.036
D
MetaRNN
Uncertain
0.60
D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
M;M;.;.;.;.;.;.;.;.
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-0.62
N;.;N;.;.;.;.;.;.;.
REVEL
Benign
0.22
Sift
Benign
0.24
T;.;T;.;.;.;.;.;.;.
Sift4G
Pathogenic
0.0
D;D;D;D;D;.;D;.;.;D
Polyphen
1.0
D;D;P;.;.;.;.;.;.;.
Vest4
0.90
MutPred
0.60
Loss of MoRF binding (P = 0.0309);Loss of MoRF binding (P = 0.0309);.;.;.;.;Loss of MoRF binding (P = 0.0309);Loss of MoRF binding (P = 0.0309);.;Loss of MoRF binding (P = 0.0309);
MVP
0.31
MPC
0.41
ClinPred
0.89
D
GERP RS
5.8
Varity_R
0.20
gMVP
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs2077556423; hg19: chr17-73263930; API