rs567167777

Variant names:

• chr17-75267575-C-A
• rs567167777
• NM_001370592.1:c.404G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-75267575-C-A
• chr17-75267575-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56

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]

ACMG classification

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
MIF4GD	NM_001370592.1	c.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
MIF4GD	ENST00000325102.13	c.404G>T	p.Arg135Leu	missense_variant	Exon 5 of 6	2	NM_001370592.1	ENSP00000321625.8

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

Other links and lift over

dbSNP: rs567167777; hg19: chr17-73263656;