15-44496419-C-T

Position:

chr15-44496419-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_016396.3(CTDSPL2):c.731C>T(p.Ala244Val) variant causes a missense change. The variant allele was found at a frequency of 0.00195 in 1,613,778 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.010 ( 33 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 25 hom. )

Consequence

CTDSPL2
NM_016396.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.12

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:

CTDSPL2 (HGNC:):

CTDSPL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004626423).

BP6

Variant 15-44496419-C-T is Benign according to our data. Variant chr15-44496419-C-T is described in ClinVar as [Benign]. Clinvar id is 714596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1599/152292) while in subpopulation AFR AF= 0.037 (1536/41536). AF 95% confidence interval is 0.0354. There are 33 homozygotes in gnomad4. There are 762 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 33 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTDSPL2	NM_016396.3 linkuse as main transcript	c.731C>T	p.Ala244Val	missense_variant	6/13	ENST00000260327.9	NP_057480.2	Q05D32-1A0A024R5Q8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CTDSPL2	ENST00000260327.9 linkuse as main transcript	c.731C>T	p.Ala244Val	missense_variant	6/13	1	NM_016396.3	ENSP00000260327.4	Q05D32-1
CTDSPL2	ENST00000558966.5 linkuse as main transcript	c.731C>T	p.Ala244Val	missense_variant	6/13	1		ENSP00000452837.1	Q05D32-1
CTDSPL2	ENST00000558373.5 linkuse as main transcript	c.515C>T	p.Ala172Val	missense_variant	4/11	1		ENSP00000453051.1	Q05D32-2
CTDSPL2	ENST00000561189.1 linkuse as main transcript	n.48C>T		non_coding_transcript_exon_variant	2/5	5

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1593

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0369

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

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:

0.0000882

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00237

AC:

594

AN:

250704

Hom.:

AF XY:

0.00158

AC XY:

214

AN XY:

135634

show subpopulations

Gnomad AFR exome

AF:

0.0346

Gnomad AMR exome

AF:

0.000695

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.00106

AC:

1546

AN:

1461486

Hom.:

Cov.:

AF XY:

0.000923

AC XY:

671

AN XY:

727060

show subpopulations

Gnomad4 AFR exome

AF:

0.0390

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.00227

GnomAD4 genome

AF:

0.0105

AC:

1599

AN:

152292

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

762

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0370

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00248

Hom.:

Bravo

AF:

0.0117

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0373

AC:

164

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00297

AC:

361

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

T;T;.

Eigen

Benign

0.031

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.89

.;D;D

MetaRNN

Benign

0.0046

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;L;.

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.030

N;N;N

REVEL

Benign

0.044

Sift

Benign

0.12

T;T;T

Sift4G

Benign

0.49

T;T;T

Polyphen

0.012

B;B;B

Vest4

0.54

MVP

0.11

MPC

0.12

ClinPred

0.013

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.096

gMVP

0.41

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