ENST00000396355.5:c.-535delC

Variant names:

• chr16-15643555-AC-A
• rs146418251
• ENST00000396355.5:c.-535delC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000396355.5(NDE1):​c.-535delC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 324,396 control chromosomes in the GnomAD database, including 141 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (141 hom., cov: 31)
  • Exomes 𝑓: 0.0010 (0 hom.)
• Consequence: NDE1 ENST00000396355.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.15
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 16-15643555-AC-A is Benign according to our data. Variant chr16-15643555-AC-A is described in ClinVar as [Likely_benign]. Clinvar id is 318023.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDE1	NM_001143979.2	c.-535delC		5_prime_UTR_variant	Exon 1 of 10		NP_001137451.1
NDE1	XM_006720897.5	c.-317delC		5_prime_UTR_variant	Exon 1 of 8		XP_006720960.1
NDE1	XM_047434258.1	c.-317delC		5_prime_UTR_variant	Exon 1 of 8		XP_047290214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDE1	ENST00000396355.5	c.-535delC		5_prime_UTR_variant	Exon 1 of 10	1		ENSP00000379643.1
NDE1	ENST00000674888.1	n.-415delC		upstream_gene_variant				ENSP00000501936.1
MIR484	ENST00000606601.3	n.*184delC		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.0233 AC: 3430 AN: 146942 Hom.: 141 Cov.: 31

Gnomad AFR AF: 0.0806

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00964

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000431

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000465

Gnomad OTH AF: 0.0171

GnomAD4 exome AF: 0.00101 AC: 179 AN: 177406 Hom.: 0 Cov.: 0 AF XY: 0.000797 AC XY: 82 AN XY: 102948

African (AFR) AF: 0.0644 AC: 75 AN: 1164

American (AMR) AF: 0.00529 AC: 17 AN: 3216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5660

East Asian (EAS) AF: 0.00 AC: 0 AN: 1276

South Asian (SAS) AF: 0.000152 AC: 6 AN: 39494

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14220

Middle Eastern (MID) AF: 0.000647 AC: 1 AN: 1546

European-Non Finnish (NFE) AF: 0.000370 AC: 38 AN: 102624

Other (OTH) AF: 0.00512 AC: 42 AN: 8206

GnomAD4 genome AF: 0.0233 AC: 3432 AN: 146990 Hom.: 141 Cov.: 31 AF XY: 0.0229 AC XY: 1635 AN XY: 71502

African (AFR) AF: 0.0805 AC: 3223 AN: 40028

American (AMR) AF: 0.00956 AC: 141 AN: 14742

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3424

East Asian (EAS) AF: 0.00 AC: 0 AN: 5088

South Asian (SAS) AF: 0.000433 AC: 2 AN: 4618

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9146

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 276

European-Non Finnish (NFE) AF: 0.000465 AC: 31 AN: 66708

Other (OTH) AF: 0.0170 AC: 35 AN: 2058

Alfa AF: 0.0177 Hom.: 11

Bravo AF: 0.0254

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Lissencephaly, Recessive Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.2
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs146418251; hg19: chr16-15737412;