2-218401670-C-A

Variant names:

• chr2-218401670-C-A
• rs2227250
• NM_021198.3:c.174C>A

Variant summary

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

The NM_021198.3(CTDSP1):​c.174C>A​(p.Ser58Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 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. S58N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CTDSP1 NM_021198.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 1 publications found

Genes affected

CTDSP1 (HGNC:21614): (CTD small phosphatase 1) This gene encodes a member of the small C-terminal domain phosphatase (SCP) family of nuclear phosphatases. These proteins play a role in transcriptional regulation through specific dephosphorylation of phosphoserine 5 within tandem heptapeptide repeats of the C-terminal domain of RNA polymerase II. The encoded protein plays a role in neuronal gene silencing in non-neuronal cells, and may also inhibit osteoblast differentiation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

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=0.11416659).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021198.3. 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
	CTDSP1	NM_021198.3	MANE Select	c.174C>A	p.Ser58Arg	missense	Exon 2 of 7	NP_067021.1	Q9GZU7-1
	CTDSP1	NM_001400269.1		c.174C>A	p.Ser58Arg	missense	Exon 2 of 6	NP_001387198.1
	CTDSP1	NM_001400270.1		c.174C>A	p.Ser58Arg	missense	Exon 2 of 6	NP_001387199.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTDSP1	ENST00000273062.7	TSL:1 MANE Select	c.174C>A	p.Ser58Arg	missense	Exon 2 of 7	ENSP00000273062.2	Q9GZU7-1
	CTDSP1	ENST00000885505.1		c.174C>A	p.Ser58Arg	missense	Exon 2 of 7	ENSP00000555564.1
	CTDSP1	ENST00000452977.6	TSL:5	c.174C>A	p.Ser58Arg	missense	Exon 2 of 7	ENSP00000404301.2	H7C270

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000414 AC: 1 AN: 241664 AF XY: 0.00000763

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000917

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452492 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 722226

African (AFR) AF: 0.00 AC: 0 AN: 33080

American (AMR) AF: 0.00 AC: 0 AN: 43032

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25486

East Asian (EAS) AF: 0.00 AC: 0 AN: 39562

South Asian (SAS) AF: 0.00 AC: 0 AN: 85288

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107514

Other (OTH) AF: 0.00 AC: 0 AN: 59920

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.8
DANN	Uncertain	0.98
DEOGEN2	Benign	0.040	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-1.4
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.073
Sift	Benign	0.091	T
Sift4G	Benign	0.17	T
Polyphen		0.031	B
Vest4		0.25
MutPred		0.33		Loss of glycosylation at S58 (P = 0.0102)
MVP		0.14
MPC		0.065
ClinPred		0.21	T
GERP RS		-5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.55

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: rs2227250; hg19: chr2-219266393;