16-15643570-CTTT-CTT

Variant names:

• chr16-15643570-CT-C
• rs796579453
• ENST00000396355:c.-512delT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001143979.2(NDE1):​c.-512delT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0678 in 244,214 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 31)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: NDE1 NM_001143979.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176

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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDE1	NM_001143979.2	c.-512delT		5_prime_UTR_variant	Exon 1 of 10		NP_001137451.1
NDE1	XM_006720897.5	c.-294delT		5_prime_UTR_variant	Exon 1 of 8		XP_006720960.1
NDE1	XM_047434258.1	c.-294delT		5_prime_UTR_variant	Exon 1 of 8		XP_047290214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDE1	ENST00000396355	c.-512delT		5_prime_UTR_variant	Exon 1 of 10	1		ENSP00000379643.1
NDE1	ENST00000674888.1	n.-400delT		upstream_gene_variant				ENSP00000501936.1

Frequencies

GnomAD3 genomes AF: 0.00145 AC: 212 AN: 146170 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00237

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000616

Gnomad ASJ AF: 0.000296

Gnomad EAS AF: 0.00613

Gnomad SAS AF: 0.000215

Gnomad FIN AF: 0.00399

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000514

Gnomad OTH AF: 0.00251

GnomAD4 exome AF: 0.167 AC: 16348 AN: 97994 Hom.: 0 Cov.: 0 AF XY: 0.165 AC XY: 9373 AN XY: 56750

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.127

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.166

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.174

GnomAD4 genome AF: 0.00147 AC: 215 AN: 146220 Hom.: 0 Cov.: 31 AF XY: 0.00167 AC XY: 119 AN XY: 71068

Gnomad4 AFR AF: 0.00242

Gnomad4 AMR AF: 0.000615

Gnomad4 ASJ AF: 0.000296

Gnomad4 EAS AF: 0.00635

Gnomad4 SAS AF: 0.000216

Gnomad4 FIN AF: 0.00399

Gnomad4 NFE AF: 0.000514

Gnomad4 OTH AF: 0.00249

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs796579453; hg19: chr16-15737427;