18-79753721-T-C

Variant names:

• chr18-79753721-T-C
• rs626169
• NM_004715.5:c.2817T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004715.5(CTDP1):​c.2817T>C​(p.Asp939Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.979 in 1,614,048 control chromosomes in the GnomAD database, including 777,656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.91 (64273 hom., cov: 33)
  • Exomes 𝑓: 0.99 (713383 hom.)
• Consequence: CTDP1 NM_004715.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.0560
• Publications: 18 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 18-79753721-T-C is Benign according to our data. Variant chr18-79753721-T-C is described in ClinVar as Benign. ClinVar VariationId is 128865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.056 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

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.2817T>C	p.Asp939Asp	synonymous	Exon 13 of 13	NP_004706.3
	CTDP1	NM_001202504.1		c.2460T>C	p.Asp820Asp	synonymous	Exon 13 of 13	NP_001189433.1
	CTDP1	NM_001318511.2		c.*46T>C		3_prime_UTR	Exon 12 of 12	NP_001305440.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTDP1	ENST00000613122.5	TSL:1 MANE Select	c.2817T>C	p.Asp939Asp	synonymous	Exon 13 of 13	ENSP00000484525.2
	CTDP1	ENST00000075430.11	TSL:1	c.*50T>C		3_prime_UTR	Exon 12 of 12	ENSP00000075430.7
	CTDP1	ENST00000591598.5	TSL:1	c.*46T>C		3_prime_UTR	Exon 12 of 12	ENSP00000465119.1

Frequencies

GnomAD3 genomes AF: 0.910 AC: 138390 AN: 152116 Hom.: 64241 Cov.: 33

Gnomad AFR AF: 0.701

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.962

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.987

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.923

GnomAD2 exomes AF: 0.971 AC: 243695 AN: 250934 AF XY: 0.977

Gnomad AFR exome AF: 0.701

Gnomad AMR exome AF: 0.980

Gnomad ASJ exome AF: 0.921

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.997

Gnomad OTH exome AF: 0.975

GnomAD4 exome AF: 0.987 AC: 1442466 AN: 1461814 Hom.: 713383 Cov.: 81 AF XY: 0.988 AC XY: 718243 AN XY: 727214

African (AFR) AF: 0.695 AC: 23270 AN: 33480

American (AMR) AF: 0.977 AC: 43695 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 23980 AN: 26136

East Asian (EAS) AF: 1.00 AC: 39697 AN: 39698

South Asian (SAS) AF: 0.989 AC: 85305 AN: 86256

European-Finnish (FIN) AF: 1.00 AC: 53350 AN: 53354

Middle Eastern (MID) AF: 0.964 AC: 5563 AN: 5768

European-Non Finnish (NFE) AF: 0.997 AC: 1109015 AN: 1112002

Other (OTH) AF: 0.970 AC: 58591 AN: 60396

GnomAD4 genome AF: 0.910 AC: 138475 AN: 152234 Hom.: 64273 Cov.: 33 AF XY: 0.913 AC XY: 67951 AN XY: 74436

African (AFR) AF: 0.701 AC: 29081 AN: 41492

American (AMR) AF: 0.963 AC: 14733 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 3164 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5163 AN: 5164

South Asian (SAS) AF: 0.987 AC: 4763 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10622 AN: 10622

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.997 AC: 67810 AN: 68034

Other (OTH) AF: 0.924 AC: 1953 AN: 2114

Alfa AF: 0.952 Hom.: 36940

Bravo AF: 0.897

Asia WGS AF: 0.971 AC: 3376 AN: 3478

EpiCase AF: 0.994

EpiControl AF: 0.994

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	2	Congenital cataracts-facial dysmorphism-neuropathy syndrome (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.0
DANN	Benign	0.59
PhyloP100		0.056
Mutation Taster		=95/5	polymorphism (auto)

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: rs626169; hg19: chr18-77513721; COSMIC: COSV50007027; COSMIC: COSV50007027;