3-129557229-C-CAGAG
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP6_Very_Strong
The NM_015103.3(PLXND1):c.5446-7_5446-6insCTCT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000299 in 1,613,906 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00031 ( 1 hom. )
Consequence
PLXND1
NM_015103.3 splice_region, splice_polypyrimidine_tract, intron
NM_015103.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.505
Genes affected
PLXND1 (HGNC:9107): (plexin D1) Enables protein domain specific binding activity. Predicted to be involved in several processes, including endothelial cell migration; nervous system development; and regulation of angiogenesis. Predicted to act upstream of or within several processes, including circulatory system development; dichotomous subdivision of terminal units involved in salivary gland branching; and positive regulation of protein binding activity. Located in lamellipodium. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 3-129557229-C-CAGAG is Benign according to our data. Variant chr3-129557229-C-CAGAG is described in ClinVar as [Likely_benign]. Clinvar id is 722559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLXND1 | NM_015103.3 | c.5446-7_5446-6insCTCT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000324093.9 | |||
PLXND1 | XM_011512588.3 | c.5446-7_5446-6insCTCT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
PLXND1 | XM_011512589.2 | c.5056-7_5056-6insCTCT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
PLXND1 | XM_011512592.1 | c.2614-7_2614-6insCTCT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLXND1 | ENST00000324093.9 | c.5446-7_5446-6insCTCT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_015103.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152180Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000955 AC: 24AN: 251260Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135826
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GnomAD4 exome AF: 0.000314 AC: 459AN: 1461726Hom.: 1 Cov.: 32 AF XY: 0.000303 AC XY: 220AN XY: 727178
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GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152180Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7AN XY: 74348
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2018 | - - |
PLXND1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 08, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at