16-15660611-G-T

Variant names:

• chr16-15660611-G-T
• rs8061376
• NM_017668.3:c.-43-4125G>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.-43-4125G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 152,038 control chromosomes in the GnomAD database, including 40,477 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 0.72 (40477 hom., cov: 31)
• Consequence: NDE1 NM_017668.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 10 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017668.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDE1	NM_017668.3	MANE Select	c.-43-4125G>T		intron	N/A	NP_060138.1
	NDE1	NM_001143979.2		c.-43-4125G>T		intron	N/A	NP_001137451.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDE1	ENST00000396354.6	TSL:1 MANE Select	c.-43-4125G>T		intron	N/A	ENSP00000379642.1
	NDE1	ENST00000396355.5	TSL:1	c.-43-4125G>T		intron	N/A	ENSP00000379643.1
	NDE1	ENST00000674995.1		c.-43-4125G>T		intron	N/A	ENSP00000502414.1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109633 AN: 151920 Hom.: 40415 Cov.: 31

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.708

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

GnomAD4 genome AF: 0.722 AC: 109756 AN: 152038 Hom.: 40477 Cov.: 31 AF XY: 0.722 AC XY: 53620 AN XY: 74298

African (AFR) AF: 0.894 AC: 37114 AN: 41502

American (AMR) AF: 0.704 AC: 10745 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 2518 AN: 3472

East Asian (EAS) AF: 0.632 AC: 3265 AN: 5166

South Asian (SAS) AF: 0.738 AC: 3555 AN: 4814

European-Finnish (FIN) AF: 0.643 AC: 6780 AN: 10538

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.639 AC: 43405 AN: 67966

Other (OTH) AF: 0.708 AC: 1494 AN: 2110

Alfa AF: 0.752 Hom.: 10291

Bravo AF: 0.732

Asia WGS AF: 0.694 AC: 2416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.17
DANN	Benign	0.30
PhyloP100		-1.2
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: rs8061376; hg19: chr16-15754468;