19-7535969-G-C
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_001166114.2(PNPLA6):āc.181G>Cā(p.Val61Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,582,828 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Synonymous variant affecting the same amino acid position (i.e. V61V) has been classified as Likely benign.
Frequency
Consequence
NM_001166114.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PNPLA6 | NM_001166114.2 | c.181G>C | p.Val61Leu | missense_variant | 1/32 | ENST00000600737.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PNPLA6 | ENST00000600737.6 | c.181G>C | p.Val61Leu | missense_variant | 1/32 | 1 | NM_001166114.2 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0121 AC: 1839AN: 152172Hom.: 40 Cov.: 32
GnomAD3 exomes AF: 0.00299 AC: 590AN: 197048Hom.: 12 AF XY: 0.00208 AC XY: 221AN XY: 106378
GnomAD4 exome AF: 0.00119 AC: 1696AN: 1430538Hom.: 41 Cov.: 32 AF XY: 0.00106 AC XY: 749AN XY: 709466
GnomAD4 genome AF: 0.0121 AC: 1846AN: 152290Hom.: 41 Cov.: 32 AF XY: 0.0116 AC XY: 860AN XY: 74454
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 39 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 29, 2020 | - - |
Mucolipidosis type IV Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Laurence-Moon syndrome;C1848745:Trichomegaly-retina pigmentary degeneration-dwarfism syndrome;C1859093:Ataxia-hypogonadism-choroidal dystrophy syndrome;C2677586:Hereditary spastic paraplegia 39 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 13, 2022 | - - |
Hereditary spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Apr 07, 2021 | - - |
Spastic Paraplegia, Recessive Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 02, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at