1-35560577-C-T

Variant names:

• chr1-35560577-C-T
• rs762979951
• NM_014284.3:c.426C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014284.3(NCDN):​c.426C>T​(p.Asp142Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NCDN NM_014284.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.601
• Publications: 0 publications found

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]

NCDN Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with infantile epileptic spasms

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=0.601 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014284.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCDN	NM_014284.3	MANE Select	c.426C>T	p.Asp142Asp	synonymous	Exon 3 of 7	NP_055099.1	Q9UBB6-1
	NCDN	NM_001014839.2		c.426C>T	p.Asp142Asp	synonymous	Exon 4 of 8	NP_001014839.1	Q9UBB6-1
	NCDN	NM_001014841.2		c.375C>T	p.Asp125Asp	synonymous	Exon 3 of 7	NP_001014841.1	Q9UBB6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCDN	ENST00000373243.7	TSL:1 MANE Select	c.426C>T	p.Asp142Asp	synonymous	Exon 3 of 7	ENSP00000362340.2	Q9UBB6-1
	NCDN	ENST00000356090.8	TSL:1	c.426C>T	p.Asp142Asp	synonymous	Exon 4 of 8	ENSP00000348394.4	Q9UBB6-1
	NCDN	ENST00000373253.7	TSL:1	c.375C>T	p.Asp125Asp	synonymous	Exon 3 of 7	ENSP00000362350.3	Q9UBB6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	8.0
DANN	Benign	0.87
PhyloP100		0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs762979951; hg19: chr1-36026178;