rs113994102

Variant names:

• chr18-79710825-C-T
• rs113994102
• NM_004715.5:c.863+389C>T

Variant summary

Our verdict is Likely pathogenic. The variant received 9 ACMG points: 10P and 1B. PM2 PP5_Very_Strong BP4

The NM_004715.5(CTDP1):​c.863+389C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★).

• Frequency: Genomes: not found (cov: 26)
• Consequence: CTDP1 NM_004715.5 intron
• Clinical Significance: Pathogenic criteria provided, multiple submitters, no conflicts P:7 O:1
• Conservation: PhyloP100: -1.29
• Publications: 7 publications found

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)

ACMG classification

Our verdict: Likely_pathogenic. The variant received 9 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 18-79710825-C-T is Pathogenic according to our data. Variant chr18-79710825-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 5301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0). . Strength limited to SUPPORTING due to the PP5.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTDP1	NM_004715.5	MANE Select	c.863+389C>T		intron	N/A	NP_004706.3
	CTDP1	NM_001318511.2		c.863+389C>T		intron	N/A	NP_001305440.1
	CTDP1	NM_048368.4		c.863+389C>T		intron	N/A	NP_430255.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTDP1	ENST00000613122.5	TSL:1 MANE Select	c.863+389C>T		intron	N/A	ENSP00000484525.2
	CTDP1	ENST00000075430.11	TSL:1	c.863+389C>T		intron	N/A	ENSP00000075430.7
	CTDP1	ENST00000591598.5	TSL:1	c.659+389C>T		intron	N/A	ENSP00000465119.1

Frequencies

GnomAD3 genomes Cov.: 26

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 26

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
4	-	-	not provided (4)
2	-	-	Congenital cataracts-facial dysmorphism-neuropathy syndrome (3)
1	-	-	Charcot-Marie-Tooth disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.7
DANN	Benign	0.65
PhyloP100		-1.3
Mutation Taster		=26/74	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		3.0
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs113994102; hg19: chr18-77470825;