15-23686450-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_002487.3(NDN):c.768C>T(p.Pro256=) 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.29

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 Likely_benign. Variant got -5 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_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.29 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDN	NM_002487.3	c.768C>T	p.Pro256=	synonymous_variant	1/1	ENST00000649030.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDN	ENST00000649030.2	c.768C>T	p.Pro256=	synonymous_variant	1/1		NM_002487.3	P1

Frequencies

GnomAD3 genomes AF: 0.00149 AC: 226 AN: 152182 Hom.: 0 Cov.: 33

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.: 1 AF XY: 0.000349 AC XY: 47 AN XY: 134568

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.: 1 Cov.: 32 AF XY: 0.000229 AC XY: 166 AN XY: 724690

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.: 0 Cov.: 33 AF XY: 0.00141 AC XY: 105 AN XY: 74470

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.: 0

Bravo AF: 0.00165

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000356

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

Dec 31, 2019

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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

Other links and lift over

dbSNP: rs142210120; hg19: chr15-23931597; COSMIC: COSV100086652;