Genetic Variant CTDSPL:p.Ile6Val (chr3-37862215-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001008392.2(CTDSPL):c.16A>G(p.Ile6Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000201 in 1,441,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000047 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

CTDSPL
NM_001008392.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.137

Variant links:

Genes affected

CTDSPL (HGNC:16890): (CTD small phosphatase like) Predicted to enable RNA polymerase II CTD heptapeptide repeat phosphatase activity. Predicted to be involved in protein dephosphorylation. Predicted to act upstream of or within negative regulation of G1/S transition of mitotic cell cycle and negative regulation of protein phosphorylation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

CTDSPL links:

ENSG00000290076 (HGNC:):

ENSG00000290076 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09221223).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTDSPL	NM_001008392.2 link	c.16A>G	p.Ile6Val	missense_variant	Exon 1 of 8	ENST00000273179.10	NP_001008393.1	O15194-1
CTDSPL	NM_005808.3 link	c.16A>G	p.Ile6Val	missense_variant	Exon 1 of 7		NP_005799.2	O15194-2
CTDSPL	XM_017005519.2 link	c.16A>G	p.Ile6Val	missense_variant	Exon 1 of 9		XP_016861008.1
CTDSPL	XM_047447182.1 link	c.16A>G	p.Ile6Val	missense_variant	Exon 1 of 8		XP_047303138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTDSPL	ENST00000273179.10 link	c.16A>G	p.Ile6Val	missense_variant	Exon 1 of 8	1	NM_001008392.2	ENSP00000273179.5		O15194-1

Frequencies

GnomAD3 genomes

AF:

0.0000469

AC:

AN:

149402

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:

0.000104

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000170

AC:

AN:

1292154

Hom.:

Cov.:

AF XY:

0.0000204

AC XY:

AN XY:

636454

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000214

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000469

AC:

AN:

149402

Hom.:

Cov.:

AF XY:

0.0000549

AC XY:

AN XY:

72894

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000104

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000604

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.16A>G (p.I6V) alteration is located in exon 1 (coding exon 1) of the CTDSPL gene. This alteration results from a A to G substitution at nucleotide position 16, causing the isoleucine (I) at amino acid position 6 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.084

.;T

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.84

T;T

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.092

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.9

L;L

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.49

N;N

REVEL

Benign

0.056

Sift

Benign

0.20

T;T

Sift4G

Benign

0.41

T;T

Polyphen

0.036

B;B

Vest4

0.17

MVP

0.25

MPC

0.59

ClinPred

0.062

GERP RS

0.10

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.064

gMVP

0.32

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over