chr1-40091336-T-C
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_000310.4(PPT1):āc.426A>Gā(p.Gln142Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: not found (cov: 31)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
PPT1
NM_000310.4 synonymous
NM_000310.4 synonymous
Scores
6
Clinical Significance
Conservation
PhyloP100: 0.362
Genes affected
PPT1 (HGNC:9325): (palmitoyl-protein thioesterase 1) The protein encoded by this gene is a small glycoprotein involved in the catabolism of lipid-modified proteins during lysosomal degradation. The encoded enzyme removes thioester-linked fatty acyl groups such as palmitate from cysteine residues. Defects in this gene are a cause of infantile neuronal ceroid lipofuscinosis 1 (CLN1, or INCL) and neuronal ceroid lipofuscinosis 4 (CLN4). Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Dec 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1411758).
BP6
Variant 1-40091336-T-C is Benign according to our data. Variant chr1-40091336-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 577912.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.362 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PPT1 | NM_000310.4 | c.426A>G | p.Gln142Gln | synonymous_variant | 4/9 | ENST00000642050.2 | NP_000301.1 | |
PPT1 | NM_001363695.2 | c.426A>G | p.Gln142Gln | synonymous_variant | 4/8 | NP_001350624.1 | ||
PPT1 | NM_001142604.2 | c.125-1824A>G | intron_variant | NP_001136076.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PPT1 | ENST00000642050.2 | c.426A>G | p.Gln142Gln | synonymous_variant | 4/9 | NM_000310.4 | ENSP00000493153.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
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31
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251272Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135818
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461600Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727112
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GnomAD4 genome Cov.: 31
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Neuronal ceroid lipofuscinosis 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 20, 2023 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
MetaRNN
Benign
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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