Variant 15-23686450-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_002487.3(NDN):c.768C>T(p.Pro256Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000371 in 1,610,292 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 1 hom. )

Consequence

NDN
NM_002487.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.29

Variant links:

Genes affected

NDN (HGNC:7675): (necdin, MAGE family member) This intronless gene is located in the Prader-Willi syndrome deletion region. It is an imprinted gene and is expressed exclusively from the paternal allele. Studies in mouse suggest that the protein encoded by this gene may suppress growth in postmitotic neurons. [provided by RefSeq, Jul 2008]

NDN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 15-23686450-G-A is Benign according to our data. Variant chr15-23686450-G-A is described in ClinVar as [Benign]. Clinvar id is 735178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.29 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDN	NM_002487.3 linkuse as main transcript	c.768C>T	p.Pro256Pro	synonymous_variant	1/1	ENST00000649030.2	NP_002478.1	Q99608X5D982

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDN	ENST00000649030.2 linkuse as main transcript	c.768C>T	p.Pro256Pro	synonymous_variant	1/1		NM_002487.3	ENSP00000497916.1		Q99608

Frequencies

GnomAD3 genomes

AF:

0.00149

AC:

226

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00475

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000459

AC:

114

AN:

248404

Hom.:

AF XY:

0.000349

AC XY:

AN XY:

134568

show subpopulations

Gnomad AFR exome

AF:

0.00416

Gnomad AMR exome

AF:

0.00108

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000979

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000250

AC:

365

AN:

1457992

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

166

AN XY:

724690

show subpopulations

Gnomad4 AFR exome

AF:

0.00459

Gnomad4 AMR exome

AF:

0.000990

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000104

Gnomad4 OTH exome

AF:

0.000764

GnomAD4 genome

AF:

0.00152

AC:

232

AN:

152300

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

105

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00488

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000491

Hom.:

Bravo

AF:

0.00165

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.67

DANN

Benign

0.76

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