chr1-151048302-C-T

Variant names:

• chr1-151048302-C-T
• NM_017860.5:c.455C>T

Variant summary

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

The NM_017860.5(C1orf56):​c.455C>T​(p.Ser152Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: C1orf56 NM_017860.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28
• Publications: 0 publications found

Genes affected

C1orf56 (HGNC:26045): (chromosome 1 open reading frame 56) This gene is a proto-oncogene whose promoter is methylated by DNA methyltransferase 3B (DNMT3B), which represses the proto-oncogene. However, a catalytically inactive isoform of DNMT3B is overexpressed in lymphomas, leading to hypomethylation of the proto-oncogene's promoter and derepression of the proto-oncogene. [provided by RefSeq, Sep 2016]

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=0.12091723).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017860.5. 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
	C1orf56	NM_017860.5	MANE Select	c.455C>T	p.Ser152Leu	missense	Exon 1 of 2	NP_060330.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf56	ENST00000368926.6	TSL:1 MANE Select	c.455C>T	p.Ser152Leu	missense	Exon 1 of 2	ENSP00000357922.5	Q9BUN1-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.99	T
PhyloP100		1.3
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.096
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.012	D
Vest4		0.34
MutPred		0.15		Loss of phosphorylation at S152 (P = 0.0105)
MVP		0.040
MPC		0.56
ClinPred		0.81	D
GERP RS		3.4
gMVP		0.098
Mutation Taster		=97/3	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

hg19: chr1-151020778; COSMIC: COSV54846343; COSMIC: COSV54846343;