rs17855830

Positions:

• chr18-79680128-T-A
• chr18-79680128-T-G

Variant summary

Our verdict is Likely benign. Variant got -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. 14/21 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

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTDP1	NM_004715.5	c.181T>A	p.Ser61Thr	missense_variant	1/13	ENST00000613122.5	NP_004706.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTDP1	ENST00000613122.5	c.181T>A	p.Ser61Thr	missense_variant	1/13	1	NM_004715.5	ENSP00000484525	P1
CTDP1	ENST00000075430.11	c.181T>A	p.Ser61Thr	missense_variant	1/12	1		ENSP00000075430
CTDP1	ENST00000591598.5			upstream_gene_variant		1		ENSP00000465119

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000293

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.050	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.76	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.16	.;N
REVEL	Benign	0.0080
Sift	Benign	0.55	.;T
Sift4G	Benign	0.56	T;T
Polyphen		0.0	B;B
Vest4		0.063
MutPred		0.22		Gain of catalytic residue at S61 (P = 0.0571);Gain of catalytic residue at S61 (P = 0.0571);
MVP		0.32
ClinPred		0.048	T
GERP RS		-7.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.040
gMVP		0.26

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

Other links and lift over

dbSNP: rs17855830; hg19: chr18-77440128;