rs2279103

Positions:

• chr18-79713127-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.13 (1585 hom., cov: 32)
  • Exomes 𝑓: 0.17 (23570 hom.)
• Consequence: CTDP1 NM_004715.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.128

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 Benign. Variant got -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 id is 259522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-79713127-C-T is described in Lovd as [Benign]. Variant chr18-79713127-C-T is described in Lovd as [Likely_benign].
• 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/exons	MANE	Protein	UniProt
CTDP1	NM_004715.5	c.1019C>T	p.Thr340Met	missense_variant	7/13	ENST00000613122.5	NP_004706.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTDP1	ENST00000613122.5	c.1019C>T	p.Thr340Met	missense_variant	7/13	1	NM_004715.5	ENSP00000484525.2
CTDP1	ENST00000075430.11	c.1019C>T	p.Thr340Met	missense_variant	7/12	1		ENSP00000075430.7
CTDP1	ENST00000591598.5	c.815C>T	p.Thr272Met	missense_variant	7/12	1		ENSP00000465119.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19131 AN: 151926 Hom.: 1586 Cov.: 32

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

GnomAD3 exomes AF: 0.136 AC: 33947 AN: 250106 Hom.: 2806 AF XY: 0.136 AC XY: 18425 AN XY: 135306

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 SAS exome AF: 0.0727

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.: 34 AF XY: 0.169 AC XY: 123002 AN XY: 726908

Gnomad4 AFR exome AF: 0.0274

Gnomad4 AMR exome AF: 0.0810

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.0930

Gnomad4 SAS exome AF: 0.0742

Gnomad4 FIN exome AF: 0.185

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.161

GnomAD4 genome AF: 0.126 AC: 19124 AN: 152044 Hom.: 1585 Cov.: 32 AF XY: 0.122 AC XY: 9098 AN XY: 74292

Gnomad4 AFR AF: 0.0328

Gnomad4 AMR AF: 0.0936

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.0677

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.108

Alfa AF: 0.165 Hom.: 5779

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

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.14
DANN	Benign	0.11
DEOGEN2	Benign	0.034	T;.;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.20	T;T;T;T
MetaRNN	Benign	0.0013	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N;N;.;.
PrimateAI	Benign	0.27	T
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	T
GERP RS		0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.0072
gMVP		0.28

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: rs2279103; hg19: chr18-77473127; COSMIC: COSV50006005;