Genetic Variant CTDSP1:p.Glu14Gly (chr2-218400131-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021198.3(CTDSP1):c.41A>G(p.Glu14Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000647 in 1,545,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. E14A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000065 ( 0 hom. )

Consequence

CTDSP1
NM_021198.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.45

Publications

0 publications found

Variant links:

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]

CTDSP1 links:

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ACMG classification

Classification was made for transcript

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=0.1477803).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTDSP1	NM_021198.3	MANE Select	c.41A>G	p.Glu14Gly	missense	Exon 1 of 7	NP_067021.1	Q9GZU7-1
CTDSP1	NM_001400269.1		c.41A>G	p.Glu14Gly	missense	Exon 1 of 6	NP_001387198.1
CTDSP1	NM_001400270.1		c.41A>G	p.Glu14Gly	missense	Exon 1 of 6	NP_001387199.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTDSP1	ENST00000273062.7	TSL:1 MANE Select	c.41A>G	p.Glu14Gly	missense	Exon 1 of 7	ENSP00000273062.2	Q9GZU7-1
CTDSP1	ENST00000885505.1		c.41A>G	p.Glu14Gly	missense	Exon 1 of 7	ENSP00000555564.1
CTDSP1	ENST00000452977.6	TSL:5	c.41A>G	p.Glu14Gly	missense	Exon 1 of 7	ENSP00000404301.2	H7C270

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151912

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000729

AC:

AN:

137170

AF XY:

0.00

show subpopulations

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:

0.0000211

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000646

AC:

AN:

1393336

Hom.:

Cov.:

AF XY:

0.00000582

AC XY:

AN XY:

687184

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31256

American (AMR)

AF:

0.00

AC:

AN:

35166

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25026

East Asian (EAS)

AF:

0.00

AC:

AN:

35550

South Asian (SAS)

AF:

0.00

AC:

AN:

78876

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4866

European-Non Finnish (NFE)

AF:

0.00000835

AC:

AN:

1077294

Other (OTH)

AF:

0.00

AC:

AN:

57714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.419

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151912

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41346

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67932

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.45

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.055

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.62

M_CAP

Pathogenic

0.57

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PhyloP100

1.5

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.13

Sift

Benign

0.16

Sift4G

Benign

0.32

Polyphen

0.0

Vest4

0.20

MutPred

0.25

Gain of MoRF binding (P = 0.0151)

MVP

0.20

MPC

0.052

ClinPred

0.51

GERP RS

2.6

PromoterAI

-0.21

Neutral

(source)

Varity_R

0.22

gMVP

0.51

Mutation Taster

=70/30

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over