rs2077556423

Variant names:

• chr17-75267849-C-G
• NM_001370592.1:c.245G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-75267849-C-G
• chr17-75267849-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>C​(p.Arg82Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,612 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. R82Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MIF4GD NM_001370592.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.44

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.245G>C	p.Arg82Pro	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.245G>C	p.Arg82Pro	missense_variant	Exon 4 of 6	2	NM_001370592.1	ENSP00000321625.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461612 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727104

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	27
DANN	Benign	0.96
DEOGEN2	Benign	0.13	T;T;.;.;.;.;.;T;T;T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	.;D;D;.;D;D;D;D;D;D
M_CAP	Benign	0.080	D
MetaRNN	Uncertain	0.73	D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.5	M;M;.;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.6	D;.;D;.;.;.;.;.;.;.
REVEL	Uncertain	0.47
Sift	Benign	0.054	T;.;T;.;.;.;.;.;.;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;.;D;.;.;D
Polyphen		1.0	D;D;D;.;.;.;.;.;.;.
Vest4		0.97
MutPred		0.66		Loss of MoRF binding (P = 0.0053);Loss of MoRF binding (P = 0.0053);.;.;.;.;Loss of MoRF binding (P = 0.0053);Loss of MoRF binding (P = 0.0053);.;Loss of MoRF binding (P = 0.0053);
MVP		0.52
MPC		0.97
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.80
gMVP		0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-73263930;