chr16-15643570-C-CT

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting

The ENST00000396355.5(NDE1):​c.-512dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0187 in 260,198 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00086 ( 0 hom., cov: 31)
Exomes 𝑓: 0.042 ( 0 hom. )

Consequence

NDE1
ENST00000396355.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.176
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00086 (126/146476) while in subpopulation AMR AF= 0.00136 (20/14664). AF 95% confidence interval is 0.000903. There are 0 homozygotes in gnomad4. There are 61 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NDE1NM_001143979.2 linkuse as main transcriptc.-512dup 5_prime_UTR_variant 1/10 NP_001137451.1
NDE1XM_006720897.5 linkuse as main transcriptc.-294dup 5_prime_UTR_variant 1/8 XP_006720960.1
NDE1XM_047434258.1 linkuse as main transcriptc.-294dup 5_prime_UTR_variant 1/8 XP_047290214.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NDE1ENST00000396355.5 linkuse as main transcriptc.-512dup 5_prime_UTR_variant 1/101 ENSP00000379643 P1Q9NXR1-2
NDE1ENST00000674888.1 linkuse as main transcript upstream_gene_variant ENSP00000501936 Q9NXR1-2

Frequencies

GnomAD3 genomes
AF:
0.000854
AC:
125
AN:
146424
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000923
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00137
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000593
Gnomad SAS
AF:
0.00107
Gnomad FIN
AF:
0.000768
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000769
Gnomad OTH
AF:
0.00101
GnomAD4 exome
AF:
0.0418
AC:
4752
AN:
113722
Hom.:
0
Cov.:
0
AF XY:
0.0409
AC XY:
2686
AN XY:
65746
show subpopulations
Gnomad4 AFR exome
AF:
0.0385
Gnomad4 AMR exome
AF:
0.0331
Gnomad4 ASJ exome
AF:
0.0386
Gnomad4 EAS exome
AF:
0.0433
Gnomad4 SAS exome
AF:
0.0398
Gnomad4 FIN exome
AF:
0.0328
Gnomad4 NFE exome
AF:
0.0437
Gnomad4 OTH exome
AF:
0.0454
GnomAD4 genome
AF:
0.000860
AC:
126
AN:
146476
Hom.:
0
Cov.:
31
AF XY:
0.000857
AC XY:
61
AN XY:
71208
show subpopulations
Gnomad4 AFR
AF:
0.000946
Gnomad4 AMR
AF:
0.00136
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000595
Gnomad4 SAS
AF:
0.00108
Gnomad4 FIN
AF:
0.000768
Gnomad4 NFE
AF:
0.000770
Gnomad4 OTH
AF:
0.000995

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Lissencephaly, Recessive Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs796579453; hg19: chr16-15737427; API