chr1-35559200-C-T

Variant names:

• chr1-35559200-C-T
• NM_014284.3:c.127C>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.95

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]

ACMG classification

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
NCDN	NM_014284.3	c.127C>T	p.Leu43Phe	missense_variant	Exon 2 of 7	ENST00000373243.7	NP_055099.1
NCDN	NM_001014839.2	c.127C>T	p.Leu43Phe	missense_variant	Exon 3 of 8		NP_001014839.1
NCDN	NM_001014841.2	c.76C>T	p.Leu26Phe	missense_variant	Exon 2 of 7		NP_001014841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCDN	ENST00000373243.7	c.127C>T	p.Leu43Phe	missense_variant	Exon 2 of 7	1	NM_014284.3	ENSP00000362340.2

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

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;