1-153645147-C-T

Variant names:

• chr1-153645147-C-T
• NM_015607.4:c.625C>T

Variant summary

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

The NM_015607.4(CHTOP):​c.625C>T​(p.Pro209Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHTOP NM_015607.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.23

Genes affected

CHTOP (HGNC:24511): (chromatin target of PRMT1) This gene encodes a small nuclear protein that is characterized by an arginine and glycine rich region. This protein may have an important role in the regulation of fetal globin gene expression and in the activation of estrogen-responsive genes. A recent study reported that this protein binds 5-hydroxymethylcytosine (5hmC) and associates with an arginine methyltransferase complex (methylosome), which promotes methylation of arginine 3 of histone H4 (H4R3) and activation of genes involved in glioblastomagenesis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Nov 2015]

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=0.14631766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHTOP	NM_015607.4	c.625C>T	p.Pro209Ser	missense_variant	Exon 6 of 6	ENST00000368694.8	NP_056422.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHTOP	ENST00000368694.8	c.625C>T	p.Pro209Ser	missense_variant	Exon 6 of 6	1	NM_015607.4	ENSP00000357683.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.628C>T (p.P210S) alteration is located in exon 6 (coding exon 5) of the CHTOP gene. This alteration results from a C to T substitution at nucleotide position 628, causing the proline (P) at amino acid position 210 to be replaced by a serine (S). 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	0.34
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	.;T;.;T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.047
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.75	T;T;T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.2	.;M;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.4	.;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.048	.;D;T;D
Sift4G	Uncertain	0.026	D;D;D;D
Polyphen		0.0010	B;B;.;.
Vest4		0.25
MutPred		0.42		.;Loss of loop (P = 0.0235);.;.;
MVP		0.23
MPC		0.63
ClinPred		0.79	D
GERP RS		4.0
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.17
gMVP		0.58

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: chr1-153617623;