rs774034064
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_001242896.3(DEPDC5):c.1014C>T(p.Pro338=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,453,550 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.000014 ( 1 hom. )
Consequence
DEPDC5
NM_001242896.3 synonymous
NM_001242896.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.70
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 Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
?
Variant 22-31802771-C-T is Benign according to our data. Variant chr22-31802771-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 414469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-2.7 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DEPDC5 | NM_001242896.3 | c.1014C>T | p.Pro338= | synonymous_variant | 15/43 | ENST00000651528.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DEPDC5 | ENST00000651528.2 | c.1014C>T | p.Pro338= | synonymous_variant | 15/43 | NM_001242896.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000537 AC: 13AN: 241936Hom.: 1 AF XY: 0.0000762 AC XY: 10AN XY: 131246
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GnomAD4 exome AF: 0.0000138 AC: 20AN: 1453550Hom.: 1 Cov.: 30 AF XY: 0.0000194 AC XY: 14AN XY: 722830
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GnomAD4 genome ? Cov.: 31
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial focal epilepsy with variable foci Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 18, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 13, 2020 | - - |
Computational scores
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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