1-151048302-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 10/17 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

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

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=0.12091723).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1orf56	NM_017860.5	c.455C>T	p.Ser152Leu	missense_variant	Exon 1 of 2	ENST00000368926.6	NP_060330.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1orf56	ENST00000368926.6	c.455C>T	p.Ser152Leu	missense_variant	Exon 1 of 2	1	NM_017860.5	ENSP00000357922.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.455C>T (p.S152L) alteration is located in exon 1 (coding exon 1) of the C1orf56 gene. This alteration results from a C to T substitution at nucleotide position 455, causing the serine (S) at amino acid position 152 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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

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