16-15686510-C-T

Variant names:

• chr16-15686510-C-T
• rs12934645
• NM_017668.3:c.387-865C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017668.3(NDE1):​c.387-865C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0525 in 985,144 control chromosomes in the GnomAD database, including 5,402 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 0.14 (3531 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1871 hom.)
• Consequence: NDE1 NM_017668.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 6 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]

NDE1 Gene-Disease associations (from GenCC):

• lissencephaly 4

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• hydranencephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• microlissencephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• NDE1-related microhydranencephaly

  Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDE1	NM_017668.3	c.387-865C>T		intron_variant	Intron 4 of 8	ENST00000396354.6	NP_060138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDE1	ENST00000396354.6	c.387-865C>T		intron_variant	Intron 4 of 8	1	NM_017668.3	ENSP00000379642.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20928 AN: 151930 Hom.: 3517 Cov.: 32

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.0719

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.00810

Gnomad SAS AF: 0.0926

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0299

Gnomad OTH AF: 0.111

GnomAD4 exome AF: 0.0369 AC: 30715 AN: 833096 Hom.: 1871 Cov.: 29 AF XY: 0.0362 AC XY: 13925 AN XY: 384710

African (AFR) AF: 0.424 AC: 6699 AN: 15782

American (AMR) AF: 0.0447 AC: 44 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.0324 AC: 167 AN: 5152

East Asian (EAS) AF: 0.0110 AC: 40 AN: 3630

South Asian (SAS) AF: 0.0834 AC: 1372 AN: 16460

European-Finnish (FIN) AF: 0.0290 AC: 8 AN: 276

Middle Eastern (MID) AF: 0.0605 AC: 98 AN: 1620

European-Non Finnish (NFE) AF: 0.0273 AC: 20811 AN: 761894

Other (OTH) AF: 0.0541 AC: 1476 AN: 27298

GnomAD4 genome AF: 0.138 AC: 20991 AN: 152048 Hom.: 3531 Cov.: 32 AF XY: 0.136 AC XY: 10114 AN XY: 74338

African (AFR) AF: 0.401 AC: 16595 AN: 41402

American (AMR) AF: 0.0716 AC: 1093 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0280 AC: 97 AN: 3468

East Asian (EAS) AF: 0.00811 AC: 42 AN: 5176

South Asian (SAS) AF: 0.0937 AC: 452 AN: 4824

European-Finnish (FIN) AF: 0.0311 AC: 329 AN: 10588

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0299 AC: 2033 AN: 68014

Other (OTH) AF: 0.117 AC: 248 AN: 2114

Alfa AF: 0.0577 Hom.: 1075

Bravo AF: 0.151

Asia WGS AF: 0.0780 AC: 270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.60
DANN	Benign	0.50
PhyloP100		0.077
Mutation Taster		=100/0	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: rs12934645; hg19: chr16-15780367;