1-153642355-G-C

Variant names:

• chr1-153642355-G-C
• rs1668656886
• NM_015607.4:c.329G>C

Variant summary

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

The NM_015607.4(CHTOP):​c.329G>C​(p.Arg110Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R110K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CHTOP NM_015607.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.17
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015607.4. 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
	CHTOP	NM_015607.4	MANE Select	c.329G>C	p.Arg110Thr	missense	Exon 4 of 6	NP_056422.2
	CHTOP	NM_001206612.2		c.332G>C	p.Arg111Thr	missense	Exon 4 of 6	NP_001193541.1	Q9Y3Y2-3
	CHTOP	NM_001317077.2		c.329G>C	p.Arg110Thr	missense	Exon 4 of 5	NP_001304006.1	Q9Y3Y2-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHTOP	ENST00000368694.8	TSL:1 MANE Select	c.329G>C	p.Arg110Thr	missense	Exon 4 of 6	ENSP00000357683.3	Q9Y3Y2-1
	CHTOP	ENST00000368690.7	TSL:1	c.332G>C	p.Arg111Thr	missense	Exon 4 of 6	ENSP00000357679.4	Q9Y3Y2-3
	CHTOP	ENST00000368687.1	TSL:1	c.254G>C	p.Arg85Thr	missense	Exon 2 of 4	ENSP00000357676.1	X6R700

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000468 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Uncertain	25
DANN	Benign	0.91
DEOGEN2	Benign	0.088	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Uncertain	0.69	D
MutationAssessor	Benign	1.8	L
PhyloP100		7.2
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-2.0	N
REVEL	Pathogenic	0.66
Sift	Benign	0.13	T
Sift4G	Uncertain	0.015	D
Polyphen		0.94	P
Vest4		0.89
MutPred		0.31		Loss of methylation at R110 (P = 0.0122)
MVP		0.83
MPC		0.93
ClinPred		0.68	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.34
gMVP		0.80
Mutation Taster		=59/41	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: rs1668656886; hg19: chr1-153614831;