rs558913954
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_ModerateBP6_ModerateBS1
The NM_001242896.3(DEPDC5):c.453C>T(p.Val151Val) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000235 in 1,614,146 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 (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000022 ( 0 hom. )
Consequence
DEPDC5
NM_001242896.3 synonymous
NM_001242896.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.87
Genes affected
DEPDC5 (HGNC:18423): (DEP domain containing 5, GATOR1 subcomplex subunit) This gene encodes a member of the IML1 family of proteins involved in G-protein signaling pathways. The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates cell growth by sensing the availability of nutrients. The protein encoded by this gene is a component of the GATOR1 (GAP activity toward Rags) complex which inhibits the amino acid-sensing branch of the mTORC1 pathway. Mutations in this gene are associated with autosomal dominant familial focal epilepsy with variable foci. A single nucleotide polymorphism in an intron of this gene has been associated with an increased risk of hepatocellular carcinoma in individuals with chronic hepatitis C virus infection. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]
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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;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
BP6
Variant 22-31778138-C-T is Benign according to our data. Variant chr22-31778138-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 414475.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000394 (6/152286) while in subpopulation EAS AF= 0.00116 (6/5194). AF 95% confidence interval is 0.000502. There are 0 homozygotes in gnomad4. There are 4 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DEPDC5 | NM_001242896.3 | c.453C>T | p.Val151Val | synonymous_variant | 8/43 | ENST00000651528.2 | NP_001229825.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DEPDC5 | ENST00000651528.2 | c.453C>T | p.Val151Val | synonymous_variant | 8/43 | NM_001242896.3 | ENSP00000498382.1 | |||
ENSG00000285404 | ENST00000646701.1 | c.369C>T | p.Val123Val | synonymous_variant | 6/21 | ENSP00000496158.1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152168Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000962 AC: 24AN: 249560Hom.: 0 AF XY: 0.0000812 AC XY: 11AN XY: 135394
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GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461860Hom.: 0 Cov.: 30 AF XY: 0.0000193 AC XY: 14AN XY: 727232
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152286Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74464
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Familial focal epilepsy with variable foci Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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