16-15686510-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-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

Gnomad4 AFR exome AF: 0.424

Gnomad4 AMR exome AF: 0.0447

Gnomad4 ASJ exome AF: 0.0324

Gnomad4 EAS exome AF: 0.0110

Gnomad4 SAS exome AF: 0.0834

Gnomad4 FIN exome AF: 0.0290

Gnomad4 NFE exome AF: 0.0273

Gnomad4 OTH exome AF: 0.0541

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

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.0716

Gnomad4 ASJ AF: 0.0280

Gnomad4 EAS AF: 0.00811

Gnomad4 SAS AF: 0.0937

Gnomad4 FIN AF: 0.0311

Gnomad4 NFE AF: 0.0299

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0419 Hom.: 448

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

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: rs12934645; hg19: chr16-15780367;