1-35560569-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_014284.3(NCDN):​c.418C>T​(p.Arg140Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R140P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

NCDN
NM_014284.3 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.859
Variant links:
Genes affected
NCDN (HGNC:17597): (neurochondrin) This gene encodes a leucine-rich cytoplasmic protein, which is highly similar to a mouse protein that negatively regulates Ca/calmodulin-dependent protein kinase II phosphorylation and may be essential for spatial learning processes. Several alternatively spliced transcript variants of this gene have been described. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.3235211).
BS2
High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NCDNNM_014284.3 linkc.418C>T p.Arg140Trp missense_variant Exon 3 of 7 ENST00000373243.7 NP_055099.1 Q9UBB6-1
NCDNNM_001014839.2 linkc.418C>T p.Arg140Trp missense_variant Exon 4 of 8 NP_001014839.1 Q9UBB6-1
NCDNNM_001014841.2 linkc.367C>T p.Arg123Trp missense_variant Exon 3 of 7 NP_001014841.1 Q9UBB6-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NCDNENST00000373243.7 linkc.418C>T p.Arg140Trp missense_variant Exon 3 of 7 1 NM_014284.3 ENSP00000362340.2 Q9UBB6-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152182
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
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:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1461124
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
726934
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000190
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152182
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 06, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.418C>T (p.R140W) alteration is located in exon 3 (coding exon 3) of the NCDN gene. This alteration results from a C to T substitution at nucleotide position 418, causing the arginine (R) at amino acid position 140 to be replaced by a tryptophan (W). 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
0.14
BayesDel_addAF
Benign
-0.0017
T
BayesDel_noAF
Benign
-0.24
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.30
.;T;T;.
Eigen
Benign
0.18
Eigen_PC
Benign
0.17
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.91
D;.;D;D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.32
T;T;T;T
MetaSVM
Benign
-0.63
T
MutationAssessor
Benign
0.69
.;N;N;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-2.4
N;N;N;N
REVEL
Benign
0.14
Sift
Uncertain
0.026
D;D;D;D
Sift4G
Uncertain
0.035
D;D;D;D
Polyphen
0.99
.;D;D;.
Vest4
0.24
MutPred
0.52
.;Gain of catalytic residue at P143 (P = 0.0249);Gain of catalytic residue at P143 (P = 0.0249);.;
MVP
0.26
MPC
2.0
ClinPred
0.86
D
GERP RS
2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.11
gMVP
0.37

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: rs1162062783; hg19: chr1-36026170; API