chr17-8460112-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_030808.5(NDEL1):ā€‹c.896A>Gā€‹(p.Asn299Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,614,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.000015 ( 0 hom. )

Consequence

NDEL1
NM_030808.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.01
Variant links:
Genes affected
NDEL1 (HGNC:17620): (nudE neurodevelopment protein 1 like 1) Enables identical protein binding activity. Involved in chromosome segregation; positive regulation of GTPase activity; and regulation of intracellular protein transport. Located in kinetochore. Biomarker of schizophrenia. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0588589).
BS2
High AC in GnomAdExome4 at 22 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NDEL1NM_030808.5 linkuse as main transcriptc.896A>G p.Asn299Ser missense_variant 8/9 ENST00000334527.12 NP_110435.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NDEL1ENST00000334527.12 linkuse as main transcriptc.896A>G p.Asn299Ser missense_variant 8/91 NM_030808.5 ENSP00000333982 P1Q9GZM8-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152226
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251416
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135878
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000217
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000150
AC:
22
AN:
1461870
Hom.:
0
Cov.:
30
AF XY:
0.0000124
AC XY:
9
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152344
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000108
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 05, 2024The c.896A>G (p.N299S) alteration is located in exon 8 (coding exon 7) of the NDEL1 gene. This alteration results from a A to G substitution at nucleotide position 896, causing the asparagine (N) at amino acid position 299 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.059
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.12
T;.
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.25
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.84
T;T
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.059
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
L;L
MutationTaster
Benign
0.94
D;D;D;D;D
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.58
N;.
REVEL
Benign
0.11
Sift
Benign
0.50
T;.
Sift4G
Benign
0.59
T;T
Polyphen
0.0
B;.
Vest4
0.13
MVP
0.50
MPC
0.30
ClinPred
0.085
T
GERP RS
3.9
Varity_R
0.061
gMVP
0.50

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: rs190118923; hg19: chr17-8363430; API