chr15-23686955-G-A
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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
NM_002487.3 missense
Scores
1
16
Clinical Significance
Conservation
PhyloP100: -0.121
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]
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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 GnomAd4 at 11 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NDN | NM_002487.3 | 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 | c.263C>T | p.Pro88Leu | missense_variant | 1/1 | NM_002487.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00584 AC: 888AN: 151944Hom.: 11 Cov.: 33
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GnomAD3 exomes AF: 0.00158 AC: 351AN: 222002Hom.: 6 AF XY: 0.00128 AC XY: 157AN XY: 122980
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GnomAD4 exome AF: 0.000564 AC: 817AN: 1448420Hom.: 3 Cov.: 32 AF XY: 0.000513 AC XY: 369AN XY: 719852
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GnomAD4 genome AF: 0.00586 AC: 891AN: 152050Hom.: 11 Cov.: 33 AF XY: 0.00573 AC XY: 426AN XY: 74334
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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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Benign
T;.
Polyphen
B;B
Vest4
MVP
MPC
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at