15-73570265-C-T
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_012428.4(NPTN):c.999G>A(p.Val333=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,614,216 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0099 ( 24 hom., cov: 33)
Exomes 𝑓: 0.0011 ( 30 hom. )
Consequence
NPTN
NM_012428.4 synonymous
NM_012428.4 synonymous
Scores
1
1
Clinical Significance
Conservation
PhyloP100: -0.392
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 Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant 15-73570265-C-T is Benign according to our data. Variant chr15-73570265-C-T is described in ClinVar as [Benign]. Clinvar id is 791101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.392 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00985 (1501/152334) while in subpopulation AFR AF= 0.0343 (1426/41560). AF 95% confidence interval is 0.0328. There are 24 homozygotes in gnomad4. There are 720 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1501 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPTN | NM_012428.4 | c.999G>A | p.Val333= | synonymous_variant | 6/9 | ENST00000345330.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPTN | ENST00000345330.9 | c.999G>A | p.Val333= | synonymous_variant | 6/9 | 1 | NM_012428.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00981 AC: 1493AN: 152216Hom.: 24 Cov.: 33
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GnomAD3 exomes AF: 0.00283 AC: 710AN: 251050Hom.: 14 AF XY: 0.00203 AC XY: 275AN XY: 135666
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GnomAD4 exome AF: 0.00107 AC: 1566AN: 1461882Hom.: 30 Cov.: 31 AF XY: 0.000917 AC XY: 667AN XY: 727240
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GnomAD4 genome AF: 0.00985 AC: 1501AN: 152334Hom.: 24 Cov.: 33 AF XY: 0.00967 AC XY: 720AN XY: 74490
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 09, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at