rs748796724

Variant names:

• chr2-218400131-A-C
• rs748796724
• NM_021198.3:c.41A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-218400131-A-C
• chr2-218400131-A-G

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.41A>C​(p.Glu14Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 1,393,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: CTDSP1 NM_021198.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.45
• 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=0.12384704).

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.41A>C	p.Glu14Ala	missense	Exon 1 of 7	NP_067021.1	Q9GZU7-1
	CTDSP1	NM_001400269.1		c.41A>C	p.Glu14Ala	missense	Exon 1 of 6	NP_001387198.1
	CTDSP1	NM_001400270.1		c.41A>C	p.Glu14Ala	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.41A>C	p.Glu14Ala	missense	Exon 1 of 7	ENSP00000273062.2	Q9GZU7-1
	CTDSP1	ENST00000885505.1		c.41A>C	p.Glu14Ala	missense	Exon 1 of 7	ENSP00000555564.1
	CTDSP1	ENST00000452977.6	TSL:5	c.41A>C	p.Glu14Ala	missense	Exon 1 of 7	ENSP00000404301.2	H7C270

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000219 AC: 3 AN: 137170 AF XY: 0.0000403

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000122 AC: 17 AN: 1393336 Hom.: 0 Cov.: 32 AF XY: 0.0000160 AC XY: 11 AN XY: 687184

African (AFR) AF: 0.00 AC: 0 AN: 31256

American (AMR) AF: 0.00 AC: 0 AN: 35166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25026

East Asian (EAS) AF: 0.0000281 AC: 1 AN: 35550

South Asian (SAS) AF: 0.000165 AC: 13 AN: 78876

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4866

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077294

Other (OTH) AF: 0.0000347 AC: 2 AN: 57714

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000840 AC: 3

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	0.20
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.78	T
M_CAP	Pathogenic	0.55	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.5
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.14
Sift	Benign	0.10	T
Sift4G	Benign	0.36	T
Polyphen		0.0	B
Vest4		0.27
MutPred		0.23		Gain of MoRF binding (P = 0.0124)
MVP		0.30
MPC		0.049
ClinPred		0.51	D
GERP RS		2.6
PromoterAI		-0.085	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.55
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs748796724; hg19: chr2-219264854;