Genetic Variant NCDN:p.Arg75Arg (chr1-35560376-G-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_014284.3(NCDN):c.225G>T(p.Arg75Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00561 in 1,614,026 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 37 hom. )

Consequence

NCDN
NM_014284.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.50

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]

NCDN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 1-35560376-G-T is Benign according to our data. Variant chr1-35560376-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1879083.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.5 with no splicing effect.

BS2

High AC in GnomAd4 at 526 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCDN	NM_014284.3 link	c.225G>T	p.Arg75Arg	synonymous_variant	Exon 3 of 7	ENST00000373243.7	NP_055099.1	Q9UBB6-1
NCDN	NM_001014839.2 link	c.225G>T	p.Arg75Arg	synonymous_variant	Exon 4 of 8		NP_001014839.1	Q9UBB6-1
NCDN	NM_001014841.2 link	c.174G>T	p.Arg58Arg	synonymous_variant	Exon 3 of 7		NP_001014841.1	Q9UBB6-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCDN	ENST00000373243.7 link	c.225G>T	p.Arg75Arg	synonymous_variant	Exon 3 of 7	1	NM_014284.3	ENSP00000362340.2		Q9UBB6-1

Frequencies

GnomAD3 genomes

AF:

0.00346

AC:

526

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.0109

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00613

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00322

AC:

810

AN:

251304

Hom.:

AF XY:

0.00327

AC XY:

444

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00893

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.000326

Gnomad NFE exome

AF:

0.00534

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00584

AC:

8535

AN:

1461672

Hom.:

Cov.:

AF XY:

0.00572

AC XY:

4159

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.000836

Gnomad4 AMR exome

AF:

0.00152

Gnomad4 ASJ exome

AF:

0.00995

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000696

Gnomad4 FIN exome

AF:

0.000789

Gnomad4 NFE exome

AF:

0.00701

Gnomad4 OTH exome

AF:

0.00450

GnomAD4 genome

AF:

0.00345

AC:

526

AN:

152354

Hom.:

Cov.:

AF XY:

0.00302

AC XY:

225

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.0109

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00613

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00563

Hom.:

Bravo

AF:

0.00327

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00534

EpiControl

AF:

0.00533

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NCDN: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.7

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over