Variant 16-15643570-C-CT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting

The ENST00000396355.5(NDE1):c.-512dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0187 in 260,198 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00086 ( 0 hom., cov: 31)

Exomes 𝑓: 0.042 ( 0 hom. )

Consequence

NDE1
ENST00000396355.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.176

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00086 (126/146476) while in subpopulation AMR AF= 0.00136 (20/14664). AF 95% confidence interval is 0.000903. There are 0 homozygotes in gnomad4. There are 61 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein
NDE1	NM_001143979.2 linkuse as main transcript	c.-512dup	5_prime_UTR_variant	1/10	NP_001137451.1
NDE1	XM_006720897.5 linkuse as main transcript	c.-294dup	5_prime_UTR_variant	1/8	XP_006720960.1
NDE1	XM_047434258.1 linkuse as main transcript	c.-294dup	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.-512dup		5_prime_UTR_variant	1/10	1		ENSP00000379643	P1	Q9NXR1-2
NDE1	ENST00000674888.1 linkuse as main transcript			upstream_gene_variant				ENSP00000501936		Q9NXR1-2

Frequencies

GnomAD3 genomes

AF:

0.000854

AC:

125

AN:

146424

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000923

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000593

Gnomad SAS

AF:

0.00107

Gnomad FIN

AF:

0.000768

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000769

Gnomad OTH

AF:

0.00101

GnomAD4 exome

AF:

0.0418

AC:

4752

AN:

113722

Hom.:

Cov.:

AF XY:

0.0409

AC XY:

2686

AN XY:

65746

show subpopulations

Gnomad4 AFR exome

AF:

0.0385

Gnomad4 AMR exome

AF:

0.0331

Gnomad4 ASJ exome

AF:

0.0386

Gnomad4 EAS exome

AF:

0.0433

Gnomad4 SAS exome

AF:

0.0398

Gnomad4 FIN exome

AF:

0.0328

Gnomad4 NFE exome

AF:

0.0437

Gnomad4 OTH exome

AF:

0.0454

GnomAD4 genome

AF:

0.000860

AC:

126

AN:

146476

Hom.:

Cov.:

AF XY:

0.000857

AC XY:

AN XY:

71208

show subpopulations

Gnomad4 AFR

AF:

0.000946

Gnomad4 AMR

AF:

0.00136

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000595

Gnomad4 SAS

AF:

0.00108

Gnomad4 FIN

AF:

0.000768

Gnomad4 NFE

AF:

0.000770

Gnomad4 OTH

AF:

0.000995

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Lissencephaly, Recessive

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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