15-23686360-G-T

Position:

• chr15-23686360-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002487.3(NDN):​c.858C>A​(p.Asp286Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,226 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NDN NM_002487.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.181597).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDN	NM_002487.3	c.858C>A	p.Asp286Glu	missense_variant	1/1	ENST00000649030.2	NP_002478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDN	ENST00000649030.2	c.858C>A	p.Asp286Glu	missense_variant	1/1		NM_002487.3	ENSP00000497916.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444226 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 716338

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.50	.;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.5	D;.
REVEL	Benign	0.058
Sift	Benign	0.030	D;.
Sift4G	Benign	0.13	T;.
Polyphen		0.031	B;B
Vest4		0.10
MutPred		0.40		Gain of disorder (P = 0.0511);Gain of disorder (P = 0.0511);
MVP		0.31
MPC		0.76
ClinPred		0.42	T
GERP RS		-1.8
Varity_R		0.20
gMVP		0.30

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;