Genetic Variant NM_001008392.2:c.235-2125T>G (chr3-37954986-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001008392.2(CTDSPL):c.235-2125T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,188 control chromosomes in the GnomAD database, including 5,885 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 5885 hom., cov: 32)

Exomes 𝑓: 0.045 ( 0 hom. )

Consequence

CTDSPL
NM_001008392.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0510

Publications

28 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008392.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CTDSPL	NM_001008392.2	MANE Select	c.235-2125T>G	intron	N/A	NP_001008393.1	O15194-1
CTDSPL	NM_001438028.1		c.235-2125T>G	intron	N/A	NP_001424957.1	H7C353
CTDSPL	NM_001438653.1		c.234+7775T>G	intron	N/A	NP_001425582.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CTDSPL	ENST00000273179.10	TSL:1 MANE Select	c.235-2125T>G	intron	N/A	ENSP00000273179.5	O15194-1
CTDSPL	ENST00000443503.6	TSL:1	c.234+7775T>G	intron	N/A	ENSP00000398288.2	O15194-2
CTDSPL	ENST00000436654.2	TSL:3	c.235-2125T>G	intron	N/A	ENSP00000409600.2	H7C353

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

36000

AN:

152048

Hom.:

5862

Cov.:

show subpopulations

Gnomad AFR

AF:

0.460

Gnomad AMI

AF:

0.0921

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.119

Gnomad EAS

AF:

0.0530

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.219

GnomAD4 exome

AF:

0.0455

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0556

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0556

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.237

AC:

36064

AN:

152166

Hom.:

5885

Cov.:

AF XY:

0.234

AC XY:

17379

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.461

AC:

19130

AN:

41502

American (AMR)

AF:

0.167

AC:

2557

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

414

AN:

3470

East Asian (EAS)

AF:

0.0531

AC:

275

AN:

5178

South Asian (SAS)

AF:

0.205

AC:

988

AN:

4820

European-Finnish (FIN)

AF:

0.113

AC:

1198

AN:

10604

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.160

AC:

10889

AN:

67994

Other (OTH)

AF:

0.216

AC:

455

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1265

2529

3794

5058

6323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<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:

0.204

Hom.:

3452

Bravo

AF:

0.252

Asia WGS

AF:

0.147

AC:

515

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

7.1

(source)

DANN

Benign

0.32

PhyloP100

-0.051

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over