18-79680128-T-A

Variant names:

• chr18-79680128-T-A
• rs17855830
• NM_004715.5:c.181T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004715.5(CTDP1):​c.181T>A​(p.Ser61Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000236 in 1,273,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S61A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: CTDP1 NM_004715.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56
• Publications: 21 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, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049955398).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTDP1	NM_004715.5	MANE Select	c.181T>A	p.Ser61Thr	missense	Exon 1 of 13	NP_004706.3
	CTDP1	NM_001318511.2		c.181T>A	p.Ser61Thr	missense	Exon 1 of 12	NP_001305440.1
	CTDP1	NM_048368.4		c.181T>A	p.Ser61Thr	missense	Exon 1 of 12	NP_430255.2	Q9Y5B0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTDP1	ENST00000613122.5	TSL:1 MANE Select	c.181T>A	p.Ser61Thr	missense	Exon 1 of 13	ENSP00000484525.2	Q9Y5B0-1
	CTDP1	ENST00000075430.11	TSL:1	c.181T>A	p.Ser61Thr	missense	Exon 1 of 12	ENSP00000075430.7	Q9Y5B0-4
	CTDP1	ENST00000857538.1		c.181T>A	p.Ser61Thr	missense	Exon 1 of 14	ENSP00000527597.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000236 AC: 3 AN: 1273816 Hom.: 0 Cov.: 57 AF XY: 0.00000160 AC XY: 1 AN XY: 626788

African (AFR) AF: 0.00 AC: 0 AN: 25600

American (AMR) AF: 0.00 AC: 0 AN: 23268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21326

East Asian (EAS) AF: 0.00 AC: 0 AN: 26698

South Asian (SAS) AF: 0.00 AC: 0 AN: 66558

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3674

European-Non Finnish (NFE) AF: 0.00000293 AC: 3 AN: 1023240

Other (OTH) AF: 0.00 AC: 0 AN: 52082

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.10
DANN	Benign	0.52
DEOGEN2	Benign	0.041	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.76	N
PhyloP100		-2.6
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.0080
Sift	Benign	0.55	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.063
MutPred		0.22		Gain of catalytic residue at S61 (P = 0.0571)
MVP		0.32
ClinPred		0.048	T
GERP RS		-7.7
PromoterAI		-0.037	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.040
gMVP		0.26
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs17855830; hg19: chr18-77440128;