XM_047446594.1:c.38C>T

Variant names:

• chr1-1615497-C-T
• rs1046631657
• XM_047446594.1:c.38C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The XM_047446594.1(MIB2):​c.38C>T​(p.Ser13Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,375,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: MIB2 XM_047446594.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 0 publications found

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]

ENSG00000272106 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09513655).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000355826.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIB2	NM_001170687.4	MANE Select	c.-266C>T		upstream_gene	N/A	NP_001164158.3	Q96AX9-1
	MIB2	NM_080875.5		c.-308C>T		upstream_gene	N/A	NP_543151.4	E9PD12
	MIB2	NM_001170686.4		c.-308C>T		upstream_gene	N/A	NP_001164157.3	Q96AX9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIB2	ENST00000958546.1		c.-266C>T		5_prime_UTR	Exon 1 of 20	ENSP00000628605.1
	MIB2	ENST00000958561.1		c.-308C>T		5_prime_UTR	Exon 1 of 20	ENSP00000628620.1
	MIB2	ENST00000958543.1		c.-308C>T		5_prime_UTR	Exon 1 of 21	ENSP00000628602.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1375298 Hom.: 0 Cov.: 32 AF XY: 0.00000147 AC XY: 1 AN XY: 678786

African (AFR) AF: 0.00 AC: 0 AN: 29944

American (AMR) AF: 0.00 AC: 0 AN: 35278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24856

East Asian (EAS) AF: 0.00 AC: 0 AN: 34816

South Asian (SAS) AF: 0.00 AC: 0 AN: 78032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4486

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1076260

Other (OTH) AF: 0.00 AC: 0 AN: 57494

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	2.2
DANN	Benign	0.86
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.0
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.063
Sift	Uncertain	0.019	D
Sift4G	Pathogenic	0.0	D
Vest4		0.091
MutPred		0.23		Loss of phosphorylation at S13 (P = 0.0068)
MVP		0.14
MPC		0.48
ClinPred		0.28	T
GERP RS		1.7
PromoterAI		0.44	Neutral
gMVP		0.056
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs1046631657; hg19: chr1-1550877;