Variant chr16-15643529-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000396355.5(NDE1):c.-564C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00291 in 361,894 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 25 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 11 hom. )

Consequence

NDE1
ENST00000396355.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.605

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 16-15643529-C-T is Benign according to our data. Variant chr16-15643529-C-T is described in ClinVar as [Benign]. Clinvar id is 318021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein
NDE1	NM_001143979.2 linkuse as main transcript	c.-564C>T	5_prime_UTR_variant	1/10	NP_001137451.1
NDE1	XM_006720897.5 linkuse as main transcript	c.-346C>T	5_prime_UTR_variant	1/8	XP_006720960.1
NDE1	XM_047434258.1 linkuse as main transcript	c.-346C>T	5_prime_UTR_variant	1/8	XP_047290214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDE1	ENST00000396355.5 linkuse as main transcript	c.-564C>T		5_prime_UTR_variant	1/10	1		ENSP00000379643	P1	Q9NXR1-2

Frequencies

GnomAD3 genomes

AF:

0.00421

AC:

638

AN:

151564

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00153

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00462

Gnomad EAS

AF:

0.0887

Gnomad SAS

AF:

0.00954

Gnomad FIN

AF:

0.0000958

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00578

GnomAD4 exome

AF:

0.00196

AC:

413

AN:

210216

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

278

AN XY:

122304

show subpopulations

Gnomad4 AFR exome

AF:

0.00189

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00423

Gnomad4 EAS exome

AF:

0.0776

Gnomad4 SAS exome

AF:

0.00303

Gnomad4 FIN exome

AF:

0.0000482

Gnomad4 NFE exome

AF:

0.000302

Gnomad4 OTH exome

AF:

0.00597

GnomAD4 genome

AF:

0.00421

AC:

639

AN:

151678

Hom.:

Cov.:

AF XY:

0.00448

AC XY:

332

AN XY:

74112

show subpopulations

Gnomad4 AFR

AF:

0.00152

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00462

Gnomad4 EAS

AF:

0.0889

Gnomad4 SAS

AF:

0.00955

Gnomad4 FIN

AF:

0.0000958

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00620

Alfa

AF:

0.0000522

Hom.:

Bravo

AF:

0.00393

Asia WGS

AF:

0.0530

AC:

185

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Lissencephaly 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.29

Position offset: -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