NM_004715.5:c.181T>G

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.181T>G(p.Ser61Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 1,421,536 control chromosomes in the GnomAD database, including 261,201 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 30995 hom., cov: 34)

Exomes 𝑓: 0.60 ( 230206 hom. )

Consequence

CTDP1
NM_004715.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.56

Publications

21 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, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

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=2.4477822E-6).

BP6

Variant 18-79680128-T-G is Benign according to our data. Variant chr18-79680128-T-G is described in ClinVar as Benign. ClinVar VariationId is 193292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004715.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTDP1	NM_004715.5	MANE Select	c.181T>G	p.Ser61Ala	missense	Exon 1 of 13	NP_004706.3
CTDP1	NM_001318511.2		c.181T>G	p.Ser61Ala	missense	Exon 1 of 12	NP_001305440.1
CTDP1	NM_048368.4		c.181T>G	p.Ser61Ala	missense	Exon 1 of 12	NP_430255.2	Q9Y5B0-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTDP1	ENST00000613122.5	TSL:1 MANE Select	c.181T>G	p.Ser61Ala	missense	Exon 1 of 13	ENSP00000484525.2	Q9Y5B0-1
CTDP1	ENST00000075430.11	TSL:1	c.181T>G	p.Ser61Ala	missense	Exon 1 of 12	ENSP00000075430.7	Q9Y5B0-4
CTDP1	ENST00000857538.1		c.181T>G	p.Ser61Ala	missense	Exon 1 of 14	ENSP00000527597.1

Frequencies

GnomAD3 genomes

AF:

0.638

AC:

96430

AN:

151236

Hom.:

30965

Cov.:

show subpopulations

Gnomad AFR

AF:

0.676

Gnomad AMI

AF:

0.656

Gnomad AMR

AF:

0.648

Gnomad ASJ

AF:

0.662

Gnomad EAS

AF:

0.580

Gnomad SAS

AF:

0.712

Gnomad FIN

AF:

0.696

Gnomad MID

AF:

0.710

Gnomad NFE

AF:

0.600

Gnomad OTH

AF:

0.648

GnomAD2 exomes

AF:

0.615

AC:

38761

AN:

63034

AF XY:

0.618

show subpopulations

Gnomad AFR exome

AF:

0.663

Gnomad AMR exome

AF:

0.615

Gnomad ASJ exome

AF:

0.635

Gnomad EAS exome

AF:

0.482

Gnomad FIN exome

AF:

0.669

Gnomad NFE exome

AF:

0.570

Gnomad OTH exome

AF:

0.610

GnomAD4 exome

AF:

0.600

AC:

762267

AN:

1270192

Hom.:

230206

Cov.:

AF XY:

0.603

AC XY:

376631

AN XY:

624728

show subpopulations

African (AFR)

AF:

0.684

AC:

17450

AN:

25500

American (AMR)

AF:

0.622

AC:

14278

AN:

22954

Ashkenazi Jewish (ASJ)

AF:

0.644

AC:

13632

AN:

21162

East Asian (EAS)

AF:

0.592

AC:

15767

AN:

26640

South Asian (SAS)

AF:

0.690

AC:

45347

AN:

65752

European-Finnish (FIN)

AF:

0.669

AC:

20892

AN:

31222

Middle Eastern (MID)

AF:

0.664

AC:

2429

AN:

3660

European-Non Finnish (NFE)

AF:

0.588

AC:

600808

AN:

1021384

Other (OTH)

AF:

0.610

AC:

31664

AN:

51918

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

17262

34524

51785

69047

86309

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17390

34780

52170

69560

86950

<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:

0.638

AC:

96506

AN:

151344

Hom.:

30995

Cov.:

AF XY:

0.645

AC XY:

47675

AN XY:

73936

show subpopulations

African (AFR)

AF:

0.677

AC:

28007

AN:

41392

American (AMR)

AF:

0.648

AC:

9874

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.662

AC:

2293

AN:

3466

East Asian (EAS)

AF:

0.579

AC:

2955

AN:

5102

South Asian (SAS)

AF:

0.711

AC:

3430

AN:

4824

European-Finnish (FIN)

AF:

0.696

AC:

7201

AN:

10352

Middle Eastern (MID)

AF:

0.712

AC:

208

AN:

292

European-Non Finnish (NFE)

AF:

0.600

AC:

40589

AN:

67686

Other (OTH)

AF:

0.646

AC:

1353

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1876

3752

5628

7504

9380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

784

1568

2352

3136

3920

<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:

0.621

Hom.:

3674

Bravo

AF:

0.632

TwinsUK

AF:

0.585

AC:

2170

ALSPAC

AF:

0.588

AC:

2267

ExAC

AF:

0.380

AC:

16026

Asia WGS

AF:

0.657

AC:

2195

AN:

3342

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Congenital cataracts-facial dysmorphism-neuropathy syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.027

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.060

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.00029

LIST_S2

Benign

0.11

MetaRNN

Benign

0.0000024

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.83

PhyloP100

-2.6

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.0

REVEL

Benign

0.0090

Sift

Benign

1.0

Sift4G

Benign

0.74

Polyphen

0.0

Vest4

0.021

ClinPred

0.015

GERP RS

-7.7

PromoterAI

-0.0092

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.028

gMVP

0.17

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over