16-15643529-C-T

Variant names:

• chr16-15643529-C-T
• rs79063947
• ENST00000396355.5:c.-564C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001143979.2(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 NM_001143979.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.605
• Publications: 1 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 -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 VariationId 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.

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.-564C>T		5_prime_UTR	Exon 1 of 10	NP_001137451.1	Q9NXR1-2
	MIR484	NR_030159.1		n.*157C>T		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDE1	ENST00000396355.5	TSL:1	c.-564C>T		5_prime_UTR	Exon 1 of 10	ENSP00000379643.1	Q9NXR1-2
	NDE1	ENST00000911227.1		c.-442C>T		5_prime_UTR	Exon 1 of 9	ENSP00000581286.1
	NDE1	ENST00000963926.1		c.-540C>T		upstream_gene	N/A	ENSP00000633985.1

Frequencies

GnomAD3 genomes AF: 0.00421 AC: 638 AN: 151564 Hom.: 25 Cov.: 32

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.: 11 Cov.: 0 AF XY: 0.00227 AC XY: 278 AN XY: 122304

African (AFR) AF: 0.00189 AC: 3 AN: 1590

American (AMR) AF: 0.00 AC: 0 AN: 4684

Ashkenazi Jewish (ASJ) AF: 0.00423 AC: 30 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: 1 AN: 20768

Middle Eastern (MID) AF: 0.000435 AC: 1 AN: 2298

European-Non Finnish (NFE) AF: 0.000302 AC: 36 AN: 119170

Other (OTH) AF: 0.00597 AC: 58 AN: 9718

GnomAD4 genome AF: 0.00421 AC: 639 AN: 151678 Hom.: 25 Cov.: 32 AF XY: 0.00448 AC XY: 332 AN XY: 74112

African (AFR) AF: 0.00152 AC: 63 AN: 41318

American (AMR) AF: 0.00190 AC: 29 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00462 AC: 16 AN: 3466

East Asian (EAS) AF: 0.0889 AC: 460 AN: 5176

South Asian (SAS) AF: 0.00955 AC: 46 AN: 4816

European-Finnish (FIN) AF: 0.0000958 AC: 1 AN: 10436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67920

Other (OTH) AF: 0.00620 AC: 13 AN: 2098

Alfa AF: 0.000125 Hom.: 0

Bravo AF: 0.00393

Asia WGS AF: 0.0530 AC: 185 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Lissencephaly 4 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.85
PhyloP100		0.60
PromoterAI		-0.012	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs79063947; hg19: chr16-15737386;