NM_001170687.4:c.115C>T

Variant names:

• chr1-1623567-C-T
• rs746032678
• NM_001170687.4:c.115C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001170687.4(MIB2):​c.115C>T​(p.Leu39Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000511 in 1,370,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. L39V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000051 (0 hom.)
• Consequence: MIB2 NM_001170687.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.87

Genes affected

MIB2 (HGNC:30577): (MIB E3 ubiquitin protein ligase 2) The protein encoded by this gene is an E3 ubiquitin protein ligase that mediates ubiquitination of proteins in the Notch signaling pathway. The encoded protein may be a suppressor of melanoma invasion. [provided by RefSeq, Mar 2017]

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=0.06897187).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIB2	NM_001170687.4	c.115C>T	p.Leu39Phe	missense_variant	Exon 3 of 20	ENST00000355826.10	NP_001164158.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIB2	ENST00000355826.10	c.115C>T	p.Leu39Phe	missense_variant	Exon 3 of 20	1	NM_001170687.4	ENSP00000348081.6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.0000489 AC: 6 AN: 122816 Hom.: 0 AF XY: 0.0000447 AC XY: 3 AN XY: 67082

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000281

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000511 AC: 7 AN: 1370690 Hom.: 0 Cov.: 34 AF XY: 0.00000593 AC XY: 4 AN XY: 674178

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000214

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000804 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000191 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	27
DANN	Benign	0.97
DEOGEN2	Benign	0.36	.;.;.;.;.;.;.;T;.
Eigen	Benign	0.14
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.069	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.78	T
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.3	N;N;N;N;N;N;N;N;N
REVEL	Benign	0.17
Sift	Benign	0.42	T;T;T;T;D;T;T;T;D
Sift4G	Uncertain	0.019	D;D;D;D;D;T;D;T;D
Vest4		0.20
MVP		0.68
MPC		1.3
ClinPred		0.23	T
GERP RS		2.2
gMVP		0.35

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: rs746032678; hg19: chr1-1558947;