dbSNP rs771690730: NDN:p.Ser316Gly (chr15-23686272-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002487.3(NDN):c.946A>G(p.Ser316Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000736 in 1,358,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

NDN
NM_002487.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.065767854).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002487.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDN	NM_002487.3	MANE Select	c.946A>G	p.Ser316Gly	missense	Exon 1 of 1	NP_002478.1	X5D982

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDN	ENST00000649030.2	MANE Select	c.946A>G	p.Ser316Gly	missense	Exon 1 of 1	ENSP00000497916.1	Q99608

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000575

AC:

AN:

173986

AF XY:

0.0000108

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.36e-7

AC:

AN:

1358618

Hom.:

Cov.:

AF XY:

0.00000151

AC XY:

AN XY:

664282

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30072

American (AMR)

AF:

0.00

AC:

AN:

28628

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19862

East Asian (EAS)

AF:

0.00

AC:

AN:

38684

South Asian (SAS)

AF:

0.0000143

AC:

AN:

69818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49036

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3682

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1063034

Other (OTH)

AF:

0.00

AC:

AN:

55802

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000842

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.23

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.66

M_CAP

Benign

0.0043

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.2

PhyloP100

1.3

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.2

REVEL

Benign

0.036

Sift

Uncertain

0.017

Sift4G

Benign

0.11

Polyphen

0.018

Vest4

0.069

MutPred

0.17

Gain of relative solvent accessibility (P = 0.005)

MVP

0.27

MPC

0.61

ClinPred

0.045

GERP RS

1.1

Varity_R

0.054

gMVP

0.35

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over