NM_001195215.2:c.547A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001195215.2(DENND1B):​c.547A>G​(p.Thr183Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000664 in 1,566,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T183P) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.000046 ( 0 hom., cov: 32)
Exomes š‘“: 0.000069 ( 0 hom. )

Consequence

DENND1B
NM_001195215.2 missense

Scores

7
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.61
Variant links:
Genes affected
DENND1B (HGNC:28404): (DENN domain containing 1B) Clathrin (see MIM 118955)-mediated endocytosis is a major mechanism for internalization of proteins and lipids. Members of the connecdenn family, such as DENND1B, function as guanine nucleotide exchange factors (GEFs) for the early endosomal small GTPase RAB35 (MIM 604199) and bind to clathrin and clathrin adaptor protein-2 (AP2; see MIM 601024). Thus, connecdenns link RAB35 activation with the clathrin machinery (Marat and McPherson, 2010 [PubMed 20154091]).[supplied by OMIM, Nov 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08127242).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DENND1BNM_001195215.2 linkc.547A>G p.Thr183Ala missense_variant Exon 9 of 23 ENST00000620048.6 NP_001182144.1 Q6P3S1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DENND1BENST00000620048.6 linkc.547A>G p.Thr183Ala missense_variant Exon 9 of 23 5 NM_001195215.2 ENSP00000479816.1 Q6P3S1-1

Frequencies

GnomAD3 genomes
AF:
0.0000461
AC:
7
AN:
151844
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000197
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000947
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000950
AC:
22
AN:
231586
Hom.:
0
AF XY:
0.0000792
AC XY:
10
AN XY:
126338
show subpopulations
Gnomad AFR exome
AF:
0.0000692
Gnomad AMR exome
AF:
0.000357
Gnomad ASJ exome
AF:
0.000103
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000758
Gnomad OTH exome
AF:
0.000180
GnomAD4 exome
AF:
0.0000686
AC:
97
AN:
1414144
Hom.:
0
Cov.:
27
AF XY:
0.0000684
AC XY:
48
AN XY:
701758
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000366
Gnomad4 ASJ exome
AF:
0.0000397
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000653
Gnomad4 OTH exome
AF:
0.000155
GnomAD4 genome
AF:
0.0000461
AC:
7
AN:
151962
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000947
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000660
Hom.:
0
Bravo
AF:
0.0000491
ExAC
AF:
0.0000497
AC:
6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.35
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.018
.;.;.;T
Eigen
Benign
0.17
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.87
D;D;D;D
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.081
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L;.;L;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-1.8
.;N;N;N
REVEL
Benign
0.13
Sift
Uncertain
0.011
.;D;D;D
Sift4G
Uncertain
0.0050
D;D;D;.
Polyphen
0.39
B;B;B;.
Vest4
0.77
MVP
0.19
MPC
0.18
ClinPred
0.070
T
GERP RS
5.4
Varity_R
0.40
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
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: rs182534827; hg19: chr1-197614834; COSMIC: COSV52473305; API