GeneBe

rs764805101

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018958.3(NPAP1):​c.391C>A​(p.Arg131Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R131G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

NPAP1
NM_018958.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.221
Variant links:
Genes affected
NPAP1 (HGNC:1190): (nuclear pore associated protein 1) This intronless retrogene is located in the Prader-Willi syndrome region on chromosome 15. This gene exhibits tissue-specific imprinting. Expression in adult testis and brain is biallelic, while expression in fetal brain is monoallelic and only from the paternal chromosome. The encoded protein is associated with the nuclear pore complex. [provided by RefSeq, Mar 2021]
PWRN1 (HGNC:33235): (Prader-Willi region non-protein coding RNA 1) This gene is located in the Prader-Willi syndrome (PWS) region of chromosome 15, which is known to undergo imprinting. The transcript is believed to be non-coding. It is bi-allelically expressed in testis and kidney, but mono-allelically expressed from the paternal allele in brain. This gene is poly-adenylated and is known to undergo alternative splicing. Transcript variants may represent part of a complex imprinting center-SNURF-SNRPN transcription unit. The contribution of this gene to the PWS phenotype is unknown, but it has been suggested that it may play a role in establishing paternal imprinting in the PWS region, perhaps by maintaining the paternal allele in an open chromatin configuration. [provided by RefSeq, Sep 2009]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03803864).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NPAP1NM_018958.3 linkc.391C>A p.Arg131Ser missense_variant Exon 1 of 1 ENST00000329468.5 NP_061831.2 Q9NZP6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NPAP1ENST00000329468.5 linkc.391C>A p.Arg131Ser missense_variant Exon 1 of 1 6 NM_018958.3 ENSP00000333735.3 Q9NZP6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.69
DANN
Benign
0.22
DEOGEN2
Benign
0.0041
T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.0086
N
LIST_S2
Benign
0.18
T
M_CAP
Benign
0.00057
T
MetaRNN
Benign
0.038
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
1.3
N
REVEL
Benign
0.035
Sift
Benign
0.87
T
Sift4G
Benign
0.89
T
Polyphen
0.0
B
Vest4
0.025
MutPred
0.20
Gain of phosphorylation at R131 (P = 0.0178);
MVP
0.030
MPC
0.074
ClinPred
0.041
T
GERP RS
1.3
Varity_R
0.049
gMVP
0.068

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-24921405; COSMIC: COSV100275235; API