Variant 15-23686955-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002487.3(NDN):c.263C>T(p.Pro88Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,600,470 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 11 hom., cov: 33)

Exomes 𝑓: 0.00056 ( 3 hom. )

Consequence

NDN
NM_002487.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.121

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022414029).

BP6

Variant 15-23686955-G-A is Benign according to our data. Variant chr15-23686955-G-A is described in ClinVar as [Benign]. Clinvar id is 713375.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-23686955-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00586 (891/152050) while in subpopulation AFR AF= 0.0204 (846/41534). AF 95% confidence interval is 0.0192. There are 11 homozygotes in gnomad4. There are 426 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDN	NM_002487.3 linkuse as main transcript	c.263C>T	p.Pro88Leu	missense_variant	1/1	ENST00000649030.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDN	ENST00000649030.2 linkuse as main transcript	c.263C>T	p.Pro88Leu	missense_variant	1/1		NM_002487.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00584

AC:

888

AN:

151944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0203

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00158

AC:

351

AN:

222002

Hom.:

AF XY:

0.00128

AC XY:

157

AN XY:

122980

show subpopulations

Gnomad AFR exome

AF:

0.0239

Gnomad AMR exome

AF:

0.00125

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000600

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000207

Gnomad OTH exome

AF:

0.000733

GnomAD4 exome

AF:

0.000564

AC:

817

AN:

1448420

Hom.:

Cov.:

AF XY:

0.000513

AC XY:

369

AN XY:

719852

show subpopulations

Gnomad4 AFR exome

AF:

0.0201

Gnomad4 AMR exome

AF:

0.00138

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000704

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000633

Gnomad4 OTH exome

AF:

0.00138

GnomAD4 genome

AF:

0.00586

AC:

891

AN:

152050

Hom.:

Cov.:

AF XY:

0.00573

AC XY:

426

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0204

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00258

Hom.:

Bravo

AF:

0.00676

ESP6500AA

AF:

0.0241

AC:

102

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.00199

AC:

232

Asia WGS

AF:

0.000867

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.71

Cadd

Benign

Dann

Benign

0.88

DEOGEN2

Benign

0.23

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.11

MetaRNN

Benign

0.0022

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

0.93

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.67

N;.

REVEL

Benign

0.015

Sift

Benign

0.095

T;.

Sift4G

Benign

0.26

T;.

Polyphen

0.0010

B;B

Vest4

0.14

MVP

0.22

MPC

0.66

ClinPred

0.0011

GERP RS

0.36

Varity_R

0.082

gMVP

0.33

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over