chr16-15643740-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000396355.5(NDE1):​c.-353A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00711 in 214,940 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0062 ( 9 hom., cov: 32)
Exomes 𝑓: 0.0094 ( 9 hom. )

Consequence

NDE1
ENST00000396355.5 5_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.145
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 Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 16-15643740-A-G is Benign according to our data. Variant chr16-15643740-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 318029.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00619 (942/152266) while in subpopulation SAS AF= 0.016 (77/4826). AF 95% confidence interval is 0.0131. There are 9 homozygotes in gnomad4. There are 485 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NDE1NM_001143979.2 linkuse as main transcriptc.-353A>G 5_prime_UTR_variant 1/10 NP_001137451.1
NDE1XM_006720897.5 linkuse as main transcriptc.-135A>G 5_prime_UTR_variant 1/8 XP_006720960.1
NDE1XM_047434258.1 linkuse as main transcriptc.-135A>G 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.-353A>G 5_prime_UTR_variant 1/101 ENSP00000379643 P1Q9NXR1-2
NDE1ENST00000674888.1 linkuse as main transcriptc.-231A>G 5_prime_UTR_variant, NMD_transcript_variant 1/10 ENSP00000501936 Q9NXR1-2

Frequencies

GnomAD3 genomes
AF:
0.00621
AC:
945
AN:
152148
Hom.:
9
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00140
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00943
Gnomad ASJ
AF:
0.0199
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0164
Gnomad FIN
AF:
0.00123
Gnomad MID
AF:
0.0253
Gnomad NFE
AF:
0.00809
Gnomad OTH
AF:
0.0115
GnomAD4 exome
AF:
0.00937
AC:
587
AN:
62674
Hom.:
9
Cov.:
0
AF XY:
0.0109
AC XY:
371
AN XY:
34150
show subpopulations
Gnomad4 AFR exome
AF:
0.00649
Gnomad4 AMR exome
AF:
0.00617
Gnomad4 ASJ exome
AF:
0.0157
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0172
Gnomad4 FIN exome
AF:
0.00251
Gnomad4 NFE exome
AF:
0.00741
Gnomad4 OTH exome
AF:
0.00492
GnomAD4 genome
AF:
0.00619
AC:
942
AN:
152266
Hom.:
9
Cov.:
32
AF XY:
0.00651
AC XY:
485
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.00135
Gnomad4 AMR
AF:
0.00942
Gnomad4 ASJ
AF:
0.0199
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0160
Gnomad4 FIN
AF:
0.00123
Gnomad4 NFE
AF:
0.00812
Gnomad4 OTH
AF:
0.0114
Alfa
AF:
0.00688
Hom.:
2
Bravo
AF:
0.00639
Asia WGS
AF:
0.00693
AC:
24
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Lissencephaly 4 Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
5.8
DANN
Benign
0.59

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: rs138559781; hg19: chr16-15737597; API