18-79680128-T-G

Position:

• chr18-79680128-T-G

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.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. 13/20 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• 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 Benign. Variant got -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 id is 193292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-79680128-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTDP1	NM_004715.5	c.181T>G	p.Ser61Ala	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>G	p.Ser61Ala	missense_variant	1/13	1	NM_004715.5	ENSP00000484525.2
CTDP1	ENST00000075430.11	c.181T>G	p.Ser61Ala	missense_variant	1/12	1		ENSP00000075430.7
CTDP1	ENST00000591598.5	c.-24T>G		upstream_gene_variant		1		ENSP00000465119.1

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96430 AN: 151236 Hom.: 30965 Cov.: 34

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

GnomAD3 exomes AF: 0.615 AC: 38761 AN: 63034 Hom.: 12321 AF XY: 0.618 AC XY: 22456 AN XY: 36352

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 SAS exome AF: 0.679

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.: 57 AF XY: 0.603 AC XY: 376631 AN XY: 624728

Gnomad4 AFR exome AF: 0.684

Gnomad4 AMR exome AF: 0.622

Gnomad4 ASJ exome AF: 0.644

Gnomad4 EAS exome AF: 0.592

Gnomad4 SAS exome AF: 0.690

Gnomad4 FIN exome AF: 0.669

Gnomad4 NFE exome AF: 0.588

Gnomad4 OTH exome AF: 0.610

GnomAD4 genome AF: 0.638 AC: 96506 AN: 151344 Hom.: 30995 Cov.: 34 AF XY: 0.645 AC XY: 47675 AN XY: 73936

Gnomad4 AFR AF: 0.677

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.711

Gnomad4 FIN AF: 0.696

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.646

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

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

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

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 10, 2018	- -

Congenital cataracts-facial dysmorphism-neuropathy syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.027
DANN	Benign	0.57
DEOGEN2	Benign	0.060	T;.
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.00029	N
LIST_S2	Benign	0.11	T;T
MetaRNN	Benign	0.0000024	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.83	N;N
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.0	.;N
REVEL	Benign	0.0090
Sift	Benign	1.0	.;T
Sift4G	Benign	0.74	T;T
Polyphen		0.0	B;B
Vest4		0.021
ClinPred		0.015	T
GERP RS		-7.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.028
gMVP		0.17

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; COSMIC: COSV50004447; COSMIC: COSV50004447;