chr15-89665942-G-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_002666.5(PLIN1):c.1210C>T(p.Leu404Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000326 in 1,502,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_002666.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLIN1 | NM_002666.5 | c.1210C>T | p.Leu404Phe | missense_variant, splice_region_variant | 9/9 | ENST00000300055.10 | |
PLIN1 | NM_001145311.2 | c.1210C>T | p.Leu404Phe | missense_variant, splice_region_variant | 9/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLIN1 | ENST00000300055.10 | c.1210C>T | p.Leu404Phe | missense_variant, splice_region_variant | 9/9 | 1 | NM_002666.5 | P1 | |
PLIN1 | ENST00000430628.2 | c.1210C>T | p.Leu404Phe | missense_variant, splice_region_variant | 9/9 | 5 | P1 | ||
PLIN1 | ENST00000560330.1 | c.124-1001C>T | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 28AN: 152182Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000156 AC: 21AN: 1350244Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 11AN XY: 668156
GnomAD4 genome ? AF: 0.000184 AC: 28AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17AN XY: 74476
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 17, 2021 | The c.1210C>T (p.L404F) alteration is located in exon 9 (coding exon 8) of the PLIN1 gene. This alteration results from a C to T substitution at nucleotide position 1210, causing the leucine (L) at amino acid position 404 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 16, 2020 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with PLIN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 842596). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces leucine with phenylalanine at codon 404 of the PLIN1 protein (p.Leu404Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at