rs587781094

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_017668.3(NDE1):c.837C>T(p.Tyr279Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0353 in 1,614,186 control chromosomes in the GnomAD database, including 1,129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 75 hom., cov: 32)

Exomes 𝑓: 0.036 ( 1054 hom. )

Consequence

NDE1
NM_017668.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.69

Publications

10 publications found

Variant links:

Genes affected

NDE1 (HGNC:17619): (nudE neurodevelopment protein 1) This gene encodes a member of the nuclear distribution E (NudE) family of proteins. The encoded protein is localized at the centrosome and interacts with other centrosome components as part of a multiprotein complex that regulates dynein function. This protein plays an essential role in microtubule organization, mitosis and neuronal migration. Mutations in this gene cause lissencephaly 4, a disorder characterized by lissencephaly, severe brain atrophy, microcephaly, and severe cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

NDE1 Gene-Disease associations (from GenCC):

lissencephaly 4
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
hydranencephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
microlissencephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
NDE1-related microhydranencephaly
Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

NDE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 16-15696750-C-T is Benign according to our data. Variant chr16-15696750-C-T is described in ClinVar as Benign. ClinVar VariationId is 138431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.69 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0268 (4074/152296) while in subpopulation NFE AF = 0.0411 (2794/68020). AF 95% confidence interval is 0.0398. There are 75 homozygotes in GnomAd4. There are 1916 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 75 AR,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDE1	NM_017668.3 link	c.837C>T	p.Tyr279Tyr	synonymous_variant	Exon 8 of 9	ENST00000396354.6	NP_060138.1	Q9NXR1-2X5DR54

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDE1	ENST00000396354.6 link	c.837C>T	p.Tyr279Tyr	synonymous_variant	Exon 8 of 9	1	NM_017668.3	ENSP00000379642.1		Q9NXR1-2

Frequencies

GnomAD3 genomes

AF:

0.0268

AC:

4078

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00743

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0270

Gnomad ASJ

AF:

0.0274

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0106

Gnomad FIN

AF:

0.0299

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0411

Gnomad OTH

AF:

0.0306

GnomAD2 exomes

AF:

0.0285

AC:

7174

AN:

251386

AF XY:

0.0293

show subpopulations

Gnomad AFR exome

AF:

0.00560

Gnomad AMR exome

AF:

0.0223

Gnomad ASJ exome

AF:

0.0222

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0309

Gnomad NFE exome

AF:

0.0415

Gnomad OTH exome

AF:

0.0331

GnomAD4 exome

AF:

0.0362

AC:

52862

AN:

1461890

Hom.:

1054

Cov.:

AF XY:

0.0357

AC XY:

25988

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00570

AC:

191

AN:

33480

American (AMR)

AF:

0.0222

AC:

991

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0251

AC:

655

AN:

26136

East Asian (EAS)

AF:

0.000126

AC:

AN:

39700

South Asian (SAS)

AF:

0.0152

AC:

1314

AN:

86258

European-Finnish (FIN)

AF:

0.0308

AC:

1643

AN:

53420

Middle Eastern (MID)

AF:

0.0250

AC:

144

AN:

5768

European-Non Finnish (NFE)

AF:

0.0413

AC:

45927

AN:

1112008

Other (OTH)

AF:

0.0330

AC:

1992

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

3366

6732

10098

13464

16830

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1666

3332

4998

6664

8330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0268

AC:

4074

AN:

152296

Hom.:

Cov.:

AF XY:

0.0257

AC XY:

1916

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00741

AC:

308

AN:

41584

American (AMR)

AF:

0.0269

AC:

411

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0274

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.0106

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0299

AC:

317

AN:

10612

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0411

AC:

2794

AN:

68020

Other (OTH)

AF:

0.0303

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

210

419

629

838

1048

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0369

Hom.:

429

Bravo

AF:

0.0257

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0401

EpiControl

AF:

0.0434

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 21, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Lissencephaly 4

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.41

(source)

DANN

Benign

0.73

PhyloP100

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over