chr1-35559200-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_014284.3(NCDN):​c.127C>T​(p.Leu43Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Consequence

NCDN
NM_014284.3 missense

Scores

2
11
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.95
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.903

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NCDNNM_014284.3 linkc.127C>T p.Leu43Phe missense_variant Exon 2 of 7 ENST00000373243.7 NP_055099.1 Q9UBB6-1
NCDNNM_001014839.2 linkc.127C>T p.Leu43Phe missense_variant Exon 3 of 8 NP_001014839.1 Q9UBB6-1
NCDNNM_001014841.2 linkc.76C>T p.Leu26Phe missense_variant Exon 2 of 7 NP_001014841.1 Q9UBB6-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NCDNENST00000373243.7 linkc.127C>T p.Leu43Phe missense_variant Exon 2 of 7 1 NM_014284.3 ENSP00000362340.2 Q9UBB6-1

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Cov.:
30

ClinVar

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

Submissions by phenotype

Neurodevelopmental disorder with infantile epileptic spasms Uncertain:1
Jul 20, 2022
Revvity Omics, Revvity
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.50
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.020
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.66
.;D;D;.
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.76
T;.;T;T
M_CAP
Benign
0.039
D
MetaRNN
Pathogenic
0.90
D;D;D;D
MetaSVM
Uncertain
-0.27
T
MutationAssessor
Benign
2.0
.;M;M;.
PrimateAI
Uncertain
0.77
T
PROVEAN
Uncertain
-2.9
D;D;D;D
REVEL
Uncertain
0.58
Sift
Benign
0.068
T;T;T;D
Sift4G
Benign
0.20
T;T;T;T
Polyphen
0.89
.;P;P;.
Vest4
0.51
MutPred
0.83
.;Loss of disorder (P = 0.1411);Loss of disorder (P = 0.1411);.;
MVP
0.72
MPC
1.3
ClinPred
0.94
D
GERP RS
4.7
Varity_R
0.61
gMVP
0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-36024801; API