Variant 17-7251258-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000574322.6(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
ENST00000574322.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.10

Variant links:

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]

CTDNEP1 links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.39C>G	p.Phe13Leu	missense_variant	1/8	ENST00000574322.6	NP_001137247.1
CTDNEP1	NM_015343.5 linkuse as main transcript	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 linkuse as main transcript	c.39C>G	p.Phe13Leu	missense_variant	1/8	1	NM_001143775.2	ENSP00000460683	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449636

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720850

show subpopulations

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

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

BayesDel_noAF

Benign

-0.28

CADD

Benign

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

LIST_S2

Benign

0.67

.;.;T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.24

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;L;L;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.89

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over