15-23686360-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_002487.3(NDN):c.858C>T(p.Asp286=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,595,954 control chromosomes in the GnomAD database, including 36,678 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2925 hom., cov: 32)
  • Exomes 𝑓: 0.21 (33753 hom.)
• Consequence: NDN NM_002487.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.354

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 15-23686360-G-A is Benign according to our data. Variant chr15-23686360-G-A is described in ClinVar as [Benign]. Clinvar id is 2796505.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.354 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDN	NM_002487.3	c.858C>T	p.Asp286=	synonymous_variant	1/1	ENST00000649030.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDN	ENST00000649030.2	c.858C>T	p.Asp286=	synonymous_variant	1/1		NM_002487.3	P1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26484 AN: 151944 Hom.: 2923 Cov.: 32

Gnomad AFR AF: 0.0418

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.186

GnomAD3 exomes AF: 0.222 AC: 52973 AN: 238980 Hom.: 6677 AF XY: 0.219 AC XY: 28434 AN XY: 129564

Gnomad AFR exome AF: 0.0391

Gnomad AMR exome AF: 0.295

Gnomad ASJ exome AF: 0.248

Gnomad EAS exome AF: 0.385

Gnomad SAS exome AF: 0.184

Gnomad FIN exome AF: 0.182

Gnomad NFE exome AF: 0.213

Gnomad OTH exome AF: 0.218

GnomAD4 exome AF: 0.211 AC: 304210 AN: 1443894 Hom.: 33753 Cov.: 34 AF XY: 0.210 AC XY: 150468 AN XY: 716100

Gnomad4 AFR exome AF: 0.0333

Gnomad4 AMR exome AF: 0.294

Gnomad4 ASJ exome AF: 0.254

Gnomad4 EAS exome AF: 0.360

Gnomad4 SAS exome AF: 0.191

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.209

Gnomad4 OTH exome AF: 0.210

GnomAD4 genome AF: 0.174 AC: 26486 AN: 152060 Hom.: 2925 Cov.: 32 AF XY: 0.177 AC XY: 13124 AN XY: 74306

Gnomad4 AFR AF: 0.0417

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.185

Alfa AF: 0.158 Hom.: 864

Bravo AF: 0.177

Asia WGS AF: 0.233 AC: 812 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 02, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	9.3
Dann	Benign	0.66

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

Other links and lift over

dbSNP: rs2192206; hg19: chr15-23931507; COSMIC: COSV59359745;