16-14945599-C-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_006985.4(NPIPA1):c.218C>T(p.Pro73Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0011 ( 0 hom., cov: 20)
Exomes 𝑓: 0.0012 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NPIPA1
NM_006985.4 missense
NM_006985.4 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: -0.691
Genes affected
NPIPA1 (HGNC:7909): (nuclear pore complex interacting protein family member A1) Predicted to be involved in mRNA transport and protein transport. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.03487408).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPIPA1 | NM_006985.4 | c.218C>T | p.Pro73Leu | missense_variant | 3/8 | ENST00000328085.10 | |
PKD1P3-NPIPA1 | NR_146231.1 | n.6425C>T | non_coding_transcript_exon_variant | 33/39 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPIPA1 | ENST00000328085.10 | c.218C>T | p.Pro73Leu | missense_variant | 3/8 | 1 | NM_006985.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 162AN: 144430Hom.: 0 Cov.: 20 FAILED QC
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GnomAD3 exomes AF: 0.000350 AC: 16AN: 45778Hom.: 0 AF XY: 0.000300 AC XY: 7AN XY: 23302
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00121 AC: 561AN: 462680Hom.: 0 Cov.: 3 AF XY: 0.00115 AC XY: 284AN XY: 245898
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00112 AC: 162AN: 144518Hom.: 0 Cov.: 20 AF XY: 0.00143 AC XY: 100AN XY: 69880
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 17, 2021 | The c.218C>T (p.P73L) alteration is located in exon 3 (coding exon 3) of the NPIPA1 gene. This alteration results from a C to T substitution at nucleotide position 218, causing the proline (P) at amino acid position 73 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
N
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MutPred
Loss of loop (P = 0.0235);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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