ENST00000396355.5:c.-564C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

1 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 links:

MIR484 (HGNC:32341): (microRNA 484) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR484 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	Protein	UniProt
NDE1	NM_001143979.2 link	c.-564C>T	5_prime_UTR_variant	Exon 1 of 10	NP_001137451.1	Q9NXR1-2X5DR54
NDE1	XM_006720897.5 link	c.-346C>T	5_prime_UTR_variant	Exon 1 of 8	XP_006720960.1
NDE1	XM_047434258.1 link	c.-346C>T	5_prime_UTR_variant	Exon 1 of 8	XP_047290214.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
NDE1	ENST00000396355.5 link	c.-564C>T	5_prime_UTR_variant	Exon 1 of 10	1	ENSP00000379643.1	Q9NXR1-2
NDE1	ENST00000674888.1 link	n.-442C>T	upstream_gene_variant			ENSP00000501936.1	Q9NXR1-2
MIR484	ENST00000606601.3 link	n.*157C>T	downstream_gene_variant		6

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

African (AFR)

AF:

0.00189

AC:

AN:

1590

American (AMR)

AF:

0.00

AC:

AN:

4684

Ashkenazi Jewish (ASJ)

AF:

0.00423

AC:

AN:

7090

East Asian (EAS)

AF:

0.0776

AC:

154

AN:

1984

South Asian (SAS)

AF:

0.00303

AC:

130

AN:

42914

European-Finnish (FIN)

AF:

0.0000482

AC:

AN:

20768

Middle Eastern (MID)

AF:

0.000435

AC:

AN:

2298

European-Non Finnish (NFE)

AF:

0.000302

AC:

AN:

119170

Other (OTH)

AF:

0.00597

AC:

AN:

9718

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00421

AC:

639

AN:

151678

Hom.:

Cov.:

AF XY:

0.00448

AC XY:

332

AN XY:

74112

show subpopulations

African (AFR)

AF:

0.00152

AC:

AN:

41318

American (AMR)

AF:

0.00190

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00462

AC:

AN:

3466

East Asian (EAS)

AF:

0.0889

AC:

460

AN:

5176

South Asian (SAS)

AF:

0.00955

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0000958

AC:

AN:

10436

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

67920

Other (OTH)

AF:

0.00620

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

126

158

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000125

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

Jan 13, 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. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

0.60

PromoterAI

-0.012

Neutral

(source)

Mutation Taster

=299/1

polymorphism (auto)

(source)

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

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ENST00000396355.5:c.-564C>T

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