rs1363467257

Variant names:

• chr2-218400134-C-A
• rs1363467257
• NM_021198.3:c.44C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-218400134-C-A
• chr2-218400134-C-T

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.44C>A​(p.Ala15Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,393,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. A15V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CTDSP1 NM_021198.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17659143).

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.44C>A	p.Ala15Asp	missense	Exon 1 of 7	NP_067021.1	Q9GZU7-1
	CTDSP1	NM_001400269.1		c.44C>A	p.Ala15Asp	missense	Exon 1 of 6	NP_001387198.1
	CTDSP1	NM_001400270.1		c.44C>A	p.Ala15Asp	missense	Exon 1 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.44C>A	p.Ala15Asp	missense	Exon 1 of 7	ENSP00000273062.2	Q9GZU7-1
	CTDSP1	ENST00000885505.1		c.44C>A	p.Ala15Asp	missense	Exon 1 of 7	ENSP00000555564.1
	CTDSP1	ENST00000452977.6	TSL:5	c.44C>A	p.Ala15Asp	missense	Exon 1 of 7	ENSP00000404301.2	H7C270

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.18e-7 AC: 1 AN: 1393432 Hom.: 0 Cov.: 32 AF XY: 0.00000146 AC XY: 1 AN XY: 687228

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31264

American (AMR) AF: 0.00 AC: 0 AN: 35152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25022

East Asian (EAS) AF: 0.00 AC: 0 AN: 35560

South Asian (SAS) AF: 0.00 AC: 0 AN: 78884

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4886

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077358

Other (OTH) AF: 0.00 AC: 0 AN: 57714

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.041
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.63	T
M_CAP	Pathogenic	0.68	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.9
PROVEAN	Benign	0.82	N
REVEL	Uncertain	0.31
Sift	Benign	0.60	T
Sift4G	Benign	0.60	T
Polyphen		0.0	B
Vest4		0.33
MutPred		0.23		Loss of MoRF binding (P = 0.0399)
MVP		0.56
MPC		0.064
ClinPred		0.17	T
GERP RS		2.9
PromoterAI		0.079	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.47
Mutation Taster		=87/13	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: rs1363467257; hg19: chr2-219264857;