chr17-7251258-G-C

Position:

• chr17-7251258-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001143775.2(CTDNEP1):​c.39C>G​(p.Phe13Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CTDNEP1 NM_001143775.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.10

Genes affected

CTDNEP1 (HGNC:19085): (CTD nuclear envelope phosphatase 1) Enables protein serine/threonine phosphatase activity. Involved in several processes, including positive regulation of triglyceride biosynthetic process; protein dephosphorylation; and protein localization to nucleus. Located in endoplasmic reticulum membrane; lipid droplet; and nuclear membrane. Part of Nem1-Spo7 phosphatase complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000262302 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24252793).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTDNEP1	NM_001143775.2	c.39C>G	p.Phe13Leu	missense_variant	1/8	ENST00000574322.6	NP_001137247.1
CTDNEP1	NM_015343.5	c.39C>G	p.Phe13Leu	missense_variant	2/9		NP_056158.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTDNEP1	ENST00000574322.6	c.39C>G	p.Phe13Leu	missense_variant	1/8	1	NM_001143775.2	ENSP00000460683.1
ENSG00000262302	ENST00000577138.1	n.224-3915C>G		intron_variant		3		ENSP00000460571.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449636 Hom.: 0 Cov.: 34 AF XY: 0.00000139 AC XY: 1 AN XY: 720850

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: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 22, 2023

The c.39C>G (p.F13L) alteration is located in exon 2 (coding exon 1) of the CTDNEP1 gene. This alteration results from a C to G substitution at nucleotide position 39, causing the phenylalanine (F) at amino acid position 13 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0053	T;T;T;T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	0.054
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.67	.;.;T;T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.24	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;L;L;.;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.38	.;.;N;.;.
REVEL	Benign	0.13
Sift	Benign	0.41	.;.;T;.;.
Sift4G	Benign	0.84	T;T;T;.;T
Polyphen		0.0030	B;B;B;.;.
Vest4		0.44
MutPred		0.43		Loss of MoRF binding (P = 0.1221);Loss of MoRF binding (P = 0.1221);Loss of MoRF binding (P = 0.1221);Loss of MoRF binding (P = 0.1221);Loss of MoRF binding (P = 0.1221);
MVP		0.78
MPC		1.3
ClinPred		0.36	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.20
gMVP		0.57

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: rs944064801; hg19: chr17-7154577; COSMIC: COSV105178775; COSMIC: COSV105178775;