NM_021198.3:c.174C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_021198.3(CTDSP1):​c.174C>T​(p.Ser58Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000767 in 1,604,748 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (9 hom., cov: 33)
  • Exomes 𝑓: 0.00041 (4 hom.)
• Consequence: CTDSP1 NM_021198.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.097).
• BP6: Variant 2-218401670-C-T is Benign according to our data. Variant chr2-218401670-C-T is described in ClinVar as Benign. ClinVar VariationId is 716070.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.44 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 9 gene

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>T	p.Ser58Ser	synonymous	Exon 2 of 7	NP_067021.1	Q9GZU7-1
	CTDSP1	NM_001400269.1		c.174C>T	p.Ser58Ser	synonymous	Exon 2 of 6	NP_001387198.1
	CTDSP1	NM_001400270.1		c.174C>T	p.Ser58Ser	synonymous	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>T	p.Ser58Ser	synonymous	Exon 2 of 7	ENSP00000273062.2	Q9GZU7-1
	CTDSP1	ENST00000885505.1		c.174C>T	p.Ser58Ser	synonymous	Exon 2 of 7	ENSP00000555564.1
	CTDSP1	ENST00000452977.6	TSL:5	c.174C>T	p.Ser58Ser	synonymous	Exon 2 of 7	ENSP00000404301.2	H7C270

Frequencies

GnomAD3 genomes AF: 0.00419 AC: 638 AN: 152132 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00113 AC: 274 AN: 241664 AF XY: 0.000923

Gnomad AFR exome AF: 0.0143

Gnomad AMR exome AF: 0.000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000519

Gnomad NFE exome AF: 0.000101

Gnomad OTH exome AF: 0.000514

GnomAD4 exome AF: 0.000407 AC: 591 AN: 1452498 Hom.: 4 Cov.: 32 AF XY: 0.000372 AC XY: 269 AN XY: 722232

African (AFR) AF: 0.0126 AC: 416 AN: 33080

American (AMR) AF: 0.000720 AC: 31 AN: 43032

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25488

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39562

South Asian (SAS) AF: 0.0000352 AC: 3 AN: 85288

European-Finnish (FIN) AF: 0.000794 AC: 42 AN: 52882

Middle Eastern (MID) AF: 0.000873 AC: 5 AN: 5728

European-Non Finnish (NFE) AF: 0.0000244 AC: 27 AN: 1107518

Other (OTH) AF: 0.00105 AC: 63 AN: 59920

GnomAD4 genome AF: 0.00420 AC: 640 AN: 152250 Hom.: 9 Cov.: 33 AF XY: 0.00390 AC XY: 290 AN XY: 74436

African (AFR) AF: 0.0142 AC: 589 AN: 41562

American (AMR) AF: 0.00183 AC: 28 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67998

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00203 Hom.: 1

Bravo AF: 0.00446

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	2.9
DANN	Benign	0.91
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs2227250; hg19: chr2-219266393;