11-9139864-C-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_015213.4(DENND5A):c.3681-10G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,612,820 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 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
DENND5A
NM_015213.4 splice_polypyrimidine_tract, intron
NM_015213.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0002566
2
Clinical Significance
Conservation
PhyloP100: -2.00
Genes affected
DENND5A (HGNC:19344): (DENN domain containing 5A) This gene encodes a DENN-domain-containing protein that functions as a RAB-activating guanine nucleotide exchange factor (GEF). This protein catalyzes the conversion of GDP to GTP and thereby converts inactive GDP-bound Rab proteins into their active GTP-bound form. The encoded protein is recruited by RAB6 onto Golgi membranes and is therefore referred to as RAB6-interacting protein 1. This protein binds with RAB39 as well. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Mutations in this gene are associated with early infantile epileptic encephalopathy-49. [provided by RefSeq, Feb 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 11-9139864-C-T is Benign according to our data. Variant chr11-9139864-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2917709.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DENND5A | NM_015213.4 | c.3681-10G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000328194.8 | NP_056028.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DENND5A | ENST00000328194.8 | c.3681-10G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_015213.4 | ENSP00000328524 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152042Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000361 AC: 9AN: 249378Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134712
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1460778Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 726558
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152042Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74262
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 13, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at