rs3784859

Positions:

• chr16-15671546-T-C
• chr16-15671546-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017668.3(NDE1):​c.237+4107T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,826 control chromosomes in the GnomAD database, including 15,172 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (15172 hom., cov: 31)
• Consequence: NDE1 NM_017668.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDE1	NM_017668.3	c.237+4107T>C		intron_variant		ENST00000396354.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDE1	ENST00000396354.6	c.237+4107T>C		intron_variant		1	NM_017668.3	P1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63779 AN: 151708 Hom.: 15173 Cov.: 31

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.453

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.420 AC: 63790 AN: 151826 Hom.: 15172 Cov.: 31 AF XY: 0.424 AC XY: 31433 AN XY: 74194

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.448

Alfa AF: 0.510 Hom.: 19823

Bravo AF: 0.410

Asia WGS AF: 0.362 AC: 1262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.9
DANN	Benign	0.62

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

Other links and lift over

dbSNP: rs3784859; hg19: chr16-15765403; COSMIC: COSV61275037; COSMIC: COSV61275037;