15-73570333-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_012428.4(NPTN):c.931C>T(p.Pro311Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
NPTN
NM_012428.4 missense
NM_012428.4 missense
Scores
5
8
6
Clinical Significance
Conservation
PhyloP100: 9.48
Genes affected
NPTN (HGNC:17867): (neuroplastin) This gene encodes a type I transmembrane protein belonging to the Ig superfamily. The protein is believed to be involved in cell-cell interactions or cell-substrate interactions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPTN | NM_012428.4 | c.931C>T | p.Pro311Ser | missense_variant | 6/9 | ENST00000345330.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPTN | ENST00000345330.9 | c.931C>T | p.Pro311Ser | missense_variant | 6/9 | 1 | NM_012428.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152188Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000800 AC: 2AN: 250146Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135282
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461822Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727210
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74348
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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 | Jun 13, 2024 | The c.931C>T (p.P311S) alteration is located in exon 6 (coding exon 6) of the NPTN gene. This alteration results from a C to T substitution at nucleotide position 931, causing the proline (P) at amino acid position 311 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.;T;.;.;T
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;T;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.;.;N;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Uncertain
T;D;.;D;T;.
Polyphen
D;.;.;D;D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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