1-153642397-G-C

Variant names:

• chr1-153642397-G-C
• rs942120799
• NM_015607.4:c.371G>C

Variant summary

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

The NM_015607.4(CHTOP):​c.371G>C​(p.Arg124Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: CHTOP NM_015607.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.70
• 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.371G>C	p.Arg124Thr	missense	Exon 4 of 6	NP_056422.2
	CHTOP	NM_001206612.2		c.374G>C	p.Arg125Thr	missense	Exon 4 of 6	NP_001193541.1	Q9Y3Y2-3
	CHTOP	NM_001317077.2		c.371G>C	p.Arg124Thr	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.371G>C	p.Arg124Thr	missense	Exon 4 of 6	ENSP00000357683.3	Q9Y3Y2-1
	CHTOP	ENST00000368690.7	TSL:1	c.374G>C	p.Arg125Thr	missense	Exon 4 of 6	ENSP00000357679.4	Q9Y3Y2-3
	CHTOP	ENST00000368687.1	TSL:1	c.296G>C	p.Arg99Thr	missense	Exon 2 of 4	ENSP00000357676.1	X6R700

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461684 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727114

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111884

Other (OTH) AF: 0.0000166 AC: 1 AN: 60384

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152208 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74358

African (AFR) AF: 0.00 AC: 0 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

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	Pathogenic	0.60
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	23
DANN	Benign	0.89
DEOGEN2	Benign	0.076	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.099	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Uncertain	0.49	D
MutationAssessor	Uncertain	2.0	M
PhyloP100		8.7
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.55
Sift	Benign	0.15	T
Sift4G	Benign	0.26	T
Polyphen		0.71	P
Vest4		0.65
MVP		0.54
MPC		0.93
ClinPred		0.59	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.34
gMVP		0.36
Mutation Taster		=64/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs942120799; hg19: chr1-153614873;