Variant chr15-44490802-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_016396.3(CTDSPL2):c.494C>G(p.Ser165Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,458 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CTDSPL2
NM_016396.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.48

Variant links:

Genes affected

CTDSPL2 (HGNC:26936): (CTD small phosphatase like 2) Enables RNA polymerase II CTD heptapeptide repeat phosphatase activity. Predicted to act upstream of or within negative regulation of BMP signaling pathway; positive regulation of protein export from nucleus; and protein dephosphorylation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CTDSPL2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity CTSL2_HUMAN

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTDSPL2	NM_016396.3 link	c.494C>G	p.Ser165Cys	missense_variant	5/13	ENST00000260327.9	NP_057480.2	Q05D32-1A0A024R5Q8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CTDSPL2	ENST00000260327.9 link	c.494C>G	p.Ser165Cys	missense_variant	5/13	1	NM_016396.3	ENSP00000260327.4	Q05D32-1
CTDSPL2	ENST00000558966.5 link	c.494C>G	p.Ser165Cys	missense_variant	5/13	1		ENSP00000452837.1	Q05D32-1
CTDSPL2	ENST00000558373.5 link	c.475+4102C>G		intron_variant		1		ENSP00000453051.1	Q05D32-2
CTDSPL2	ENST00000558791.5 link	c.494C>G	p.Ser165Cys	missense_variant, splice_region_variant	5/5	4		ENSP00000453612.1	H0YMH7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460458

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726568

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2024

The c.494C>G (p.S165C) alteration is located in exon 5 (coding exon 4) of the CTDSPL2 gene. This alteration results from a C to G substitution at nucleotide position 494, causing the serine (S) at amino acid position 165 to be replaced by a cysteine (C). 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

Uncertain

0.38

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.073

T;T;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

.;D;D

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.48

T;D;T

MetaSVM

Uncertain

-0.21

MutationAssessor

Uncertain

2.0

M;.;M

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.6

N;D;N

REVEL

Uncertain

0.43

Sift

Benign

0.092

T;D;T

Sift4G

Benign

0.090

T;D;T

Polyphen

0.89

P;.;P

Vest4

0.70

MutPred

0.30

Loss of glycosylation at S165 (P = 0.0264);Loss of glycosylation at S165 (P = 0.0264);Loss of glycosylation at S165 (P = 0.0264);

MVP

0.22

MPC

0.48

ClinPred

0.84

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.57

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

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