NM_002487.3:c.723A>C

Variant names:

• chr15-23686495-T-G
• rs774758735
• NM_002487.3:c.723A>C

Variant summary

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

The NM_002487.3(NDN):​c.723A>C​(p.Gln241His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 33)
• Consequence: NDN NM_002487.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170

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=0.24787825).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDN	NM_002487.3	c.723A>C	p.Gln241His	missense_variant	Exon 1 of 1	ENST00000649030.2	NP_002478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDN	ENST00000649030.2	c.723A>C	p.Gln241His	missense_variant	Exon 1 of 1		NM_002487.3	ENSP00000497916.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.28	T;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.54	.;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.5	N;.
REVEL	Benign	0.076
Sift	Uncertain	0.019	D;.
Sift4G	Benign	0.094	T;.
Polyphen		0.072	B;B
Vest4		0.24
MutPred		0.61		Gain of ubiquitination at K246 (P = 0.0797);Gain of ubiquitination at K246 (P = 0.0797);
MVP		0.36
MPC		1.5
ClinPred		0.73	D
GERP RS		-0.014
Varity_R		0.099
gMVP		0.59

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: rs774758735; hg19: chr15-23931642;