11-9139800-T-A
Position:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_015213.4(DENND5A):c.3735A>T(p.Ala1245=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,944 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 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
DENND5A
NM_015213.4 synonymous
NM_015213.4 synonymous
Scores
1
1
12
Clinical Significance
Conservation
PhyloP100: 0.0740
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09019211).
BP6
Variant 11-9139800-T-A is Benign according to our data. Variant chr11-9139800-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2811390.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.3735A>T | p.Ala1245= | synonymous_variant | 23/23 | ENST00000328194.8 | NP_056028.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DENND5A | ENST00000328194.8 | c.3735A>T | p.Ala1245= | synonymous_variant | 23/23 | 1 | NM_015213.4 | ENSP00000328524 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152096Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
2
AN:
152096
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251142Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135728
GnomAD3 exomes
AF:
AC:
1
AN:
251142
Hom.:
AF XY:
AC XY:
1
AN XY:
135728
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461848Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727228
GnomAD4 exome
AF:
AC:
1
AN:
1461848
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
727228
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152096Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74290
GnomAD4 genome
AF:
AC:
2
AN:
152096
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74290
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ESP6500AA
AF:
AC:
2
ESP6500EA
AF:
AC:
0
ExAC
AF:
AC:
1
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 | Jul 25, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;N
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Vest4
MVP
ClinPred
T
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at