16-15649332-TTGTC-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP6BS1

The NM_001143979.2(NDE1):​c.-165-12_-165-9delCTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000538 in 152,330 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

NDE1
NM_001143979.2 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.569
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 Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 16-15649332-TTGTC-T is Benign according to our data. Variant chr16-15649332-TTGTC-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 318035.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000538 (82/152330) while in subpopulation NFE AF= 0.000735 (50/68030). AF 95% confidence interval is 0.000572. There are 0 homozygotes in gnomad4. There are 38 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NDE1NM_001143979.2 linkc.-165-12_-165-9delCTGT intron_variant Intron 1 of 9 NP_001137451.1 Q9NXR1-2X5DR54
NDE1XM_006720897.5 linkc.53+5409_53+5412delCTGT intron_variant Intron 1 of 7 XP_006720960.1
NDE1XM_047434258.1 linkc.53+5409_53+5412delCTGT intron_variant Intron 1 of 7 XP_047290214.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NDE1ENST00000396355.5 linkc.-165-15_-165-12delTGTC intron_variant Intron 1 of 9 1 ENSP00000379643.1 Q9NXR1-2
NDE1ENST00000674888.1 linkn.-44+5406_-44+5409delTGTC intron_variant Intron 1 of 9 ENSP00000501936.1 Q9NXR1-2

Frequencies

GnomAD3 genomes
AF:
0.000539
AC:
82
AN:
152212
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.00490
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000282
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000735
Gnomad OTH
AF:
0.00143
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
30
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
24
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000538
AC:
82
AN:
152330
Hom.:
0
Cov.:
33
AF XY:
0.000510
AC XY:
38
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.00490
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000282
Gnomad4 NFE
AF:
0.000735
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000702
Hom.:
0
Bravo
AF:
0.000450

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Lissencephaly, Recessive Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not provided Benign:1
May 24, 2018
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs757466932; hg19: chr16-15743189; API