18-79713127-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004715.5(CTDP1):c.1019C>T(p.Thr340Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,613,250 control chromosomes in the GnomAD database, including 25,155 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T340T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.13 ( 1585 hom., cov: 32)

Exomes 𝑓: 0.17 ( 23570 hom. )

Consequence

CTDP1
NM_004715.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.128

Publications

44 publications found

Variant links:

Genes affected

CTDP1 (HGNC:2498): (CTD phosphatase subunit 1) This gene encodes a protein which interacts with the carboxy-terminus of the RAP74 subunit of transcription initiation factor TFIIF, and functions as a phosphatase that processively dephosphorylates the C-terminus of POLR2A (a subunit of RNA polymerase II), making it available for initiation of gene expression. Mutations in this gene are associated with congenital cataracts, facial dysmorphism and neuropathy syndrome (CCFDN). Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2011]

CTDP1 Gene-Disease associations (from GenCC):

congenital cataracts-facial dysmorphism-neuropathy syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

CTDP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012694299).

BP6

Variant 18-79713127-C-T is Benign according to our data. Variant chr18-79713127-C-T is described in ClinVar as Benign. ClinVar VariationId is 259522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTDP1	NM_004715.5 link	c.1019C>T	p.Thr340Met	missense_variant	Exon 7 of 13	ENST00000613122.5	NP_004706.3	Q9Y5B0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CTDP1	ENST00000613122.5 link	c.1019C>T	p.Thr340Met	missense_variant	Exon 7 of 13	1	NM_004715.5	ENSP00000484525.2	Q9Y5B0-1
CTDP1	ENST00000075430.11 link	c.1019C>T	p.Thr340Met	missense_variant	Exon 7 of 12	1		ENSP00000075430.7	Q9Y5B0-4
CTDP1	ENST00000591598.5 link	c.815C>T	p.Thr272Met	missense_variant	Exon 7 of 12	1		ENSP00000465119.1	K7EJD2

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19131

AN:

151926

Hom.:

1586

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0329

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.0937

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.0677

Gnomad FIN

AF:

0.177

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.187

Gnomad OTH

AF:

0.110

GnomAD2 exomes

AF:

0.136

AC:

33947

AN:

250106

AF XY:

0.136

show subpopulations

Gnomad AFR exome

AF:

0.0309

Gnomad AMR exome

AF:

0.0791

Gnomad ASJ exome

AF:

0.106

Gnomad EAS exome

AF:

0.123

Gnomad FIN exome

AF:

0.182

Gnomad NFE exome

AF:

0.181

Gnomad OTH exome

AF:

0.138

GnomAD4 exome

AF:

0.172

AC:

251721

AN:

1461206

Hom.:

23570

Cov.:

AF XY:

0.169

AC XY:

123002

AN XY:

726908

show subpopulations

African (AFR)

AF:

0.0274

AC:

916

AN:

33476

American (AMR)

AF:

0.0810

AC:

3621

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

2698

AN:

26132

East Asian (EAS)

AF:

0.0930

AC:

3692

AN:

39698

South Asian (SAS)

AF:

0.0742

AC:

6401

AN:

86236

European-Finnish (FIN)

AF:

0.185

AC:

9851

AN:

53368

Middle Eastern (MID)

AF:

0.0711

AC:

410

AN:

5766

European-Non Finnish (NFE)

AF:

0.193

AC:

214431

AN:

1111450

Other (OTH)

AF:

0.161

AC:

9701

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

10307

20613

30920

41226

51533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7374

14748

22122

29496

36870

<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:

0.126

AC:

19124

AN:

152044

Hom.:

1585

Cov.:

AF XY:

0.122

AC XY:

9098

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.0328

AC:

1362

AN:

41480

American (AMR)

AF:

0.0936

AC:

1431

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

349

AN:

3472

East Asian (EAS)

AF:

0.119

AC:

617

AN:

5178

South Asian (SAS)

AF:

0.0677

AC:

326

AN:

4812

European-Finnish (FIN)

AF:

0.177

AC:

1865

AN:

10540

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.187

AC:

12738

AN:

67962

Other (OTH)

AF:

0.108

AC:

229

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

826

1652

2478

3304

4130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<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:

0.157

Hom.:

8034

Bravo

AF:

0.116

TwinsUK

AF:

0.206

AC:

765

ALSPAC

AF:

0.190

AC:

732

ESP6500AA

AF:

0.0386

AC:

170

ESP6500EA

AF:

0.179

AC:

1538

ExAC

AF:

0.136

AC:

16531

Asia WGS

AF:

0.0860

AC:

301

AN:

3478

EpiCase

AF:

0.172

EpiControl

AF:

0.168

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.14

(source)

DANN

Benign

0.11

DEOGEN2

Benign

0.034

T;.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.20

T;T;T;T

MetaRNN

Benign

0.0013

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

N;N;.;.

PhyloP100

0.13

PrimateAI

Benign

0.27

PROVEAN

Benign

0.85

.;N;.;.

REVEL

Benign

0.0040

Sift

Benign

0.40

.;T;.;.

Sift4G

Benign

0.20

T;T;T;T

Polyphen

0.10

B;B;.;.

Vest4

0.026

MPC

0.88

ClinPred

0.00064

GERP RS

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.0072

gMVP

0.28

Mutation Taster

=98/2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over