rs567167777

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001370592.1(MIF4GD):​c.404G>T​(p.Arg135Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R135Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

MIF4GD
NM_001370592.1 missense

Scores

1
1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.56
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19051567).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MIF4GDNM_001370592.1 linkc.404G>T p.Arg135Leu missense_variant Exon 5 of 6 ENST00000325102.13 NP_001357521.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MIF4GDENST00000325102.13 linkc.404G>T p.Arg135Leu missense_variant Exon 5 of 6 2 NM_001370592.1 ENSP00000321625.8 A9UHW6-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
20
DANN
Benign
0.94
DEOGEN2
Benign
0.055
T;T;.;.;.;.;.;.;T;.
Eigen
Benign
-0.35
Eigen_PC
Benign
-0.20
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.90
.;D;D;.;D;D;D;D;D;D
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.19
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
L;L;.;.;.;.;.;.;.;.
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-1.9
N;.;N;.;.;.;.;.;.;.
REVEL
Benign
0.10
Sift
Benign
0.41
T;.;T;.;.;.;.;.;.;.
Sift4G
Benign
0.10
T;T;T;T;T;T;.;T;.;.
Polyphen
0.25
B;B;B;.;.;.;.;.;.;.
Vest4
0.79
MutPred
0.40
Loss of catalytic residue at R135 (P = 0.1174);Loss of catalytic residue at R135 (P = 0.1174);.;.;.;.;.;Loss of catalytic residue at R135 (P = 0.1174);Loss of catalytic residue at R135 (P = 0.1174);.;
MVP
0.31
MPC
0.31
ClinPred
0.34
T
GERP RS
2.8
Varity_R
0.063
gMVP
0.63

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: rs567167777; hg19: chr17-73263656; API