Variant 17-7251218-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001143775.2(CTDNEP1):c.79C>T(p.Leu27Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000552 in 1,450,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CTDNEP1
NM_001143775.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.86

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:

ENSG00000262302 (HGNC:):

ENSG00000262302 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22488183).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTDNEP1	NM_001143775.2 link	c.79C>T	p.Leu27Phe	missense_variant	1/8	ENST00000574322.6	NP_001137247.1	O95476
CTDNEP1	NM_015343.5 link	c.79C>T	p.Leu27Phe	missense_variant	2/9		NP_056158.2	O95476

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTDNEP1	ENST00000574322.6 link	c.79C>T	p.Leu27Phe	missense_variant	1/8	1	NM_001143775.2	ENSP00000460683.1		O95476
ENSG00000262302	ENST00000577138.1 link	n.224-3875C>T		intron_variant		3		ENSP00000460571.1		I3L3M4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000844

AC:

AN:

236962

Hom.:

AF XY:

0.00000773

AC XY:

AN XY:

129340

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000580

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000930

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000552

AC:

AN:

1450586

Hom.:

Cov.:

AF XY:

0.00000693

AC XY:

AN XY:

721330

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000258

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.0000500

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000826

AC:

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

Apr 01, 2024

The c.79C>T (p.L27F) alteration is located in exon 2 (coding exon 1) of the CTDNEP1 gene. This alteration results from a C to T substitution at nucleotide position 79, causing the leucine (L) at amino acid position 27 to be replaced by a phenylalanine (F). 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

Benign

0.091

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0088

T;T;T;T;.

Eigen

Benign

-0.084

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.79

.;.;T;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.22

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;N;N;.;.

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.74

.;.;N;.;.

REVEL

Benign

0.056

Sift

Benign

0.15

.;.;T;.;.

Sift4G

Benign

0.14

T;T;T;.;T

Polyphen

0.0010

B;B;B;.;.

Vest4

0.20

MutPred

0.48

Gain of MoRF binding (P = 0.2365);Gain of MoRF binding (P = 0.2365);Gain of MoRF binding (P = 0.2365);Gain of MoRF binding (P = 0.2365);Gain of MoRF binding (P = 0.2365);

MVP

0.17

MPC

1.2

ClinPred

0.22

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.19

gMVP

0.43

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