3-57641668-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_152678.3(DENND6A):c.1117G>A(p.Asp373Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000484 in 1,612,268 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000048 ( 0 hom. )
Consequence
DENND6A
NM_152678.3 missense
NM_152678.3 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 7.48
Genes affected
DENND6A (HGNC:26635): (DENN domain containing 6A) Enables guanyl-nucleotide exchange factor activity. Involved in positive regulation of cell-cell adhesion mediated by cadherin. Located in recycling endosome. [provided by Alliance of Genome Resources, Apr 2022]
PDE12 (HGNC:25386): (phosphodiesterase 12) Enables 3'-5'-exoribonuclease activity. Involved in several processes, including RNA metabolic process; cellular response to cytokine stimulus; and regulation of mitochondrial mRNA stability. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DENND6A | ENST00000311128.10 | c.1117G>A | p.Asp373Asn | missense_variant | 12/20 | 1 | NM_152678.3 | ENSP00000311401.5 | ||
DENND6A | ENST00000477344.1 | c.421G>A | p.Asp141Asn | missense_variant | 5/6 | 3 | ENSP00000419334.1 | |||
DENND6A-AS1 | ENST00000470427.1 | n.69+12790C>T | intron_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000527 AC: 8AN: 151904Hom.: 0 Cov.: 30
GnomAD3 genomes
AF:
AC:
8
AN:
151904
Hom.:
Cov.:
30
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: 0.0000598 AC: 15AN: 250894Hom.: 0 AF XY: 0.0000590 AC XY: 8AN XY: 135656
GnomAD3 exomes
AF:
AC:
15
AN:
250894
Hom.:
AF XY:
AC XY:
8
AN XY:
135656
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: 0.0000479 AC: 70AN: 1460364Hom.: 0 Cov.: 30 AF XY: 0.0000440 AC XY: 32AN XY: 726494
GnomAD4 exome
AF:
AC:
70
AN:
1460364
Hom.:
Cov.:
30
AF XY:
AC XY:
32
AN XY:
726494
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: 0.0000527 AC: 8AN: 151904Hom.: 0 Cov.: 30 AF XY: 0.0000674 AC XY: 5AN XY: 74168
GnomAD4 genome
AF:
AC:
8
AN:
151904
Hom.:
Cov.:
30
AF XY:
AC XY:
5
AN XY:
74168
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
4
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 24, 2024 | The c.1117G>A (p.D373N) alteration is located in exon 12 (coding exon 12) of the DENND6A gene. This alteration results from a G to A substitution at nucleotide position 1117, causing the aspartic acid (D) at amino acid position 373 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Loss of ubiquitination at K375 (P = 0.0438);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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