rs1002567339

Variant names:

• chr2-218404372-A-T
• rs1002567339
• NM_021198.3:c.733A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-218404372-A-T
• chr2-218404372-A-C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_021198.3(CTDSP1):​c.733A>T​(p.Ser245Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CTDSP1 NM_021198.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.44
• Publications: 0 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.812

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.733A>T	p.Ser245Cys	missense	Exon 7 of 7	NP_067021.1	Q9GZU7-1
	CTDSP1	NM_001400271.1		c.757A>T	p.Ser253Cys	missense	Exon 7 of 7	NP_001387200.1
	CTDSP1	NM_001400272.1		c.733A>T	p.Ser245Cys	missense	Exon 7 of 7	NP_001387201.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTDSP1	ENST00000273062.7	TSL:1 MANE Select	c.733A>T	p.Ser245Cys	missense	Exon 7 of 7	ENSP00000273062.2	Q9GZU7-1
	CTDSP1	ENST00000885505.1		c.781A>T	p.Ser261Cys	missense	Exon 7 of 7	ENSP00000555564.1
	CTDSP1	ENST00000452977.6	TSL:5	c.754A>T	p.Ser252Cys	missense	Exon 7 of 7	ENSP00000404301.2	H7C270

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251396 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461416 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727028

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111606

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 34

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	Benign	0.14
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		7.4
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.80
MutPred		0.56		Loss of disorder (P = 0.0542)
MVP		0.45
MPC		2.2
ClinPred		0.98	D
GERP RS		4.1
Varity_R		0.73
gMVP		0.94
Mutation Taster		=47/53	disease causing

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: rs1002567339; hg19: chr2-219269095;