rs626169

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr18-79753721-T-A
• chr18-79753721-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004715.5(CTDP1):​c.2817T>A​(p.Asp939Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 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. D939G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CTDP1 NM_004715.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12224388).

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>A	p.Asp939Glu	missense	Exon 13 of 13	NP_004706.3
	CTDP1	NM_001202504.1		c.2460T>A	p.Asp820Glu	missense	Exon 13 of 13	NP_001189433.1
	CTDP1	NM_001318511.2		c.*46T>A		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>A	p.Asp939Glu	missense	Exon 13 of 13	ENSP00000484525.2
	CTDP1	ENST00000075430.11	TSL:1	c.*50T>A		3_prime_UTR	Exon 12 of 12	ENSP00000075430.7
	CTDP1	ENST00000591598.5	TSL:1	c.*46T>A		3_prime_UTR	Exon 12 of 12	ENSP00000465119.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 81

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	10
DANN	Uncertain	1.0
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.056
PrimateAI	Uncertain	0.67	T
REVEL	Benign	0.088
Sift4G	Benign	0.28	T
Polyphen		0.77	P
Vest4		0.13
MutPred		0.53		Loss of catalytic residue at G941 (P = 0.1888)
MVP		0.46
MPC		0.47
ClinPred		0.79	D
GERP RS		2.1
Varity_R		0.045
gMVP		0.11

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;