16-15643570-CTTT-CTTTTT

Variant names:

• chr16-15643570-C-CTT
• rs796579453
• ENST00000396355.5:c.-513_-512dupTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001143979.2(NDE1):​c.-513_-512dupTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 121,330 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: NDE1 NM_001143979.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143979.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDE1	NM_001143979.2		c.-513_-512dupTT		5_prime_UTR	Exon 1 of 10	NP_001137451.1	Q9NXR1-2
	MIR484	NR_030159.1		n.*198_*199insTT		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDE1	ENST00000396355.5	TSL:1	c.-513_-512dupTT		5_prime_UTR	Exon 1 of 10	ENSP00000379643.1	Q9NXR1-2
	NDE1	ENST00000911227.1		c.-391_-390dupTT		5_prime_UTR	Exon 1 of 9	ENSP00000581286.1
	NDE1	ENST00000963926.1		c.-499_-498insTT		upstream_gene	N/A	ENSP00000633985.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.000115 AC: 14 AN: 121330 Hom.: 0 Cov.: 0 AF XY: 0.0000570 AC XY: 4 AN XY: 70226

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 760

American (AMR) AF: 0.000600 AC: 1 AN: 1666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3510

East Asian (EAS) AF: 0.00 AC: 0 AN: 822

South Asian (SAS) AF: 0.000110 AC: 3 AN: 27294

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 786

European-Non Finnish (NFE) AF: 0.000138 AC: 10 AN: 72362

Other (OTH) AF: 0.00 AC: 0 AN: 5752

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.18

Splicing

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

Other links and lift over

dbSNP: rs796579453; hg19: chr16-15737427;