NM_020774.4:c.14G>C

Variant names:

• chr18-21741597-G-C
• NM_020774.4:c.14G>C

Variant summary

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

The NM_020774.4(MIB1):​c.14G>C​(p.Arg5Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MIB1 NM_020774.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.20

Genes affected

MIB1 (HGNC:21086): (MIB E3 ubiquitin protein ligase 1) This gene encodes a protein containing multiple ankyrin repeats and RING finger domains that functions as an E3 ubiquitin ligase. The encoded protein positively regulates Notch signaling by ubiquitinating the Notch receptors, thereby facilitating their endocytosis. This protein may also promote the ubiquitination and degradation of death-associated protein kinase 1 (DAPK1). [provided by RefSeq, Jun 2013]

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
MIB1	NM_020774.4	c.14G>C	p.Arg5Pro	missense_variant	Exon 1 of 21	ENST00000261537.7	NP_065825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIB1	ENST00000261537.7	c.14G>C	p.Arg5Pro	missense_variant	Exon 1 of 21	1	NM_020774.4	ENSP00000261537.6
MIB1	ENST00000578646.5	n.168-24175G>C		intron_variant	Intron 1 of 20	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.83	T
M_CAP	Pathogenic	0.89	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.42
MutPred		0.31		Loss of MoRF binding (P = 2e-04);
MVP		0.70
MPC		1.2
ClinPred		0.95	D
GERP RS		3.3
Varity_R		0.56
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-19321558;