rs767558450

Variant names:

• chr17-75267796-C-A
• rs767558450
• NM_001370592.1:c.298G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-75267796-C-A
• chr17-75267796-C-G

Variant summary

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

The NM_001370592.1(MIF4GD):​c.298G>T​(p.Gly100Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,692 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G100R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: MIF4GD NM_001370592.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.67

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 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
MIF4GD	NM_001370592.1	c.298G>T	p.Gly100Cys	missense_variant	Exon 4 of 6	ENST00000325102.13	NP_001357521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIF4GD	ENST00000325102.13	c.298G>T	p.Gly100Cys	missense_variant	Exon 4 of 6	2	NM_001370592.1	ENSP00000321625.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251030 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135716

Gnomad AFR exome AF: 0.00

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: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461692 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 727156

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: 0.00000719

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	26
DANN	Benign	0.96
DEOGEN2	Benign	0.054	T;T;.;.;.;.;.;T;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	.;D;D;.;D;D;D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.48	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.2	N;.;N;.;.;.;.;.;.
REVEL	Benign	0.29
Sift	Benign	0.037	D;.;D;.;.;.;.;.;.
Sift4G	Benign	0.080	T;T;T;T;T;.;T;.;.
Polyphen		0.93	P;P;D;.;.;.;.;.;.
Vest4		0.55
MutPred		0.59		Loss of MoRF binding (P = 0.082);Loss of MoRF binding (P = 0.082);.;.;.;.;Loss of MoRF binding (P = 0.082);Loss of MoRF binding (P = 0.082);.;
MVP		0.55
MPC		0.81
ClinPred		0.94	D
GERP RS		5.6
Varity_R		0.32
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs767558450; hg19: chr17-73263877;