chr11-9139800-T-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_ModerateBP6_ModerateBP7BS1

The NM_015213.4(DENND5A):ā€‹c.3735A>Gā€‹(p.Ala1245=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 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 (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.000012 ( 0 hom. )

Consequence

DENND5A
NM_015213.4 synonymous

Scores

1
1
12

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0740
Variant links:
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 Benign. Variant got -7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07341379).
BP6
Variant 11-9139800-T-C is Benign according to our data. Variant chr11-9139800-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1985701.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.074 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0000123 (18/1461848) while in subpopulation SAS AF= 0.000197 (17/86252). AF 95% confidence interval is 0.000125. There are 0 homozygotes in gnomad4_exome. There are 13 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DENND5ANM_015213.4 linkuse as main transcriptc.3735A>G p.Ala1245= synonymous_variant 23/23 ENST00000328194.8 NP_056028.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DENND5AENST00000328194.8 linkuse as main transcriptc.3735A>G p.Ala1245= synonymous_variant 23/231 NM_015213.4 ENSP00000328524 P3Q6IQ26-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152096
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
251142
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135728
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1461848
Hom.:
0
Cov.:
31
AF XY:
0.0000179
AC XY:
13
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000197
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152096
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74290
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000494
AC:
6
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJul 29, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
6.6
DANN
Benign
0.89
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.24
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.29
T
M_CAP
Benign
0.0051
T
MetaRNN
Benign
0.073
T
MetaSVM
Benign
-0.90
T
MutationTaster
Benign
1.0
D;D;N
PROVEAN
Benign
0.080
N
REVEL
Benign
0.047
Sift
Pathogenic
0.0
D
Vest4
0.22
MutPred
0.41
Gain of MoRF binding (P = 4e-04);
MVP
0.29
ClinPred
0.062
T
GERP RS
1.9

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs371344666; hg19: chr11-9161347; API