NM_001366683.2:c.474C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001366683.2(DOCK9):​c.474C>T​(p.Val158Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 1,612,214 control chromosomes in the GnomAD database, including 23,051 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 1851 hom., cov: 33)
Exomes 𝑓: 0.17 ( 21200 hom. )

Consequence

DOCK9
NM_001366683.2 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.571

Publications

18 publications found
Variant links:
Genes affected
DOCK9 (HGNC:14132): (dedicator of cytokinesis 9) Enables cadherin binding activity. Predicted to be involved in positive regulation of GTPase activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]
DOCK9 Gene-Disease associations (from GenCC):
  • keratoconus
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP7
Synonymous conserved (PhyloP=-0.571 with no splicing effect.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DOCK9NM_001366683.2 linkc.474C>T p.Val158Val synonymous_variant Exon 5 of 53 ENST00000682017.1 NP_001353612.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DOCK9ENST00000682017.1 linkc.474C>T p.Val158Val synonymous_variant Exon 5 of 53 NM_001366683.2 ENSP00000507034.1 A0A804HIE8

Frequencies

GnomAD3 genomes
AF:
0.149
AC:
22616
AN:
152032
Hom.:
1850
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0890
Gnomad AMI
AF:
0.160
Gnomad AMR
AF:
0.160
Gnomad ASJ
AF:
0.171
Gnomad EAS
AF:
0.194
Gnomad SAS
AF:
0.212
Gnomad FIN
AF:
0.157
Gnomad MID
AF:
0.206
Gnomad NFE
AF:
0.171
Gnomad OTH
AF:
0.173
GnomAD2 exomes
AF:
0.181
AC:
45108
AN:
248996
AF XY:
0.181
show subpopulations
Gnomad AFR exome
AF:
0.0883
Gnomad AMR exome
AF:
0.236
Gnomad ASJ exome
AF:
0.174
Gnomad EAS exome
AF:
0.199
Gnomad FIN exome
AF:
0.164
Gnomad NFE exome
AF:
0.172
Gnomad OTH exome
AF:
0.170
GnomAD4 exome
AF:
0.167
AC:
244533
AN:
1460064
Hom.:
21200
Cov.:
31
AF XY:
0.169
AC XY:
122546
AN XY:
726410
show subpopulations
African (AFR)
AF:
0.0849
AC:
2840
AN:
33462
American (AMR)
AF:
0.225
AC:
10055
AN:
44686
Ashkenazi Jewish (ASJ)
AF:
0.173
AC:
4527
AN:
26122
East Asian (EAS)
AF:
0.242
AC:
9618
AN:
39674
South Asian (SAS)
AF:
0.204
AC:
17593
AN:
86152
European-Finnish (FIN)
AF:
0.167
AC:
8896
AN:
53376
Middle Eastern (MID)
AF:
0.199
AC:
1143
AN:
5758
European-Non Finnish (NFE)
AF:
0.162
AC:
179809
AN:
1110528
Other (OTH)
AF:
0.167
AC:
10052
AN:
60306
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.453
Heterozygous variant carriers
0
9821
19642
29463
39284
49105
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
6330
12660
18990
25320
31650
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.149
AC:
22633
AN:
152150
Hom.:
1851
Cov.:
33
AF XY:
0.149
AC XY:
11115
AN XY:
74384
show subpopulations
African (AFR)
AF:
0.0893
AC:
3706
AN:
41506
American (AMR)
AF:
0.161
AC:
2453
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
0.171
AC:
593
AN:
3468
East Asian (EAS)
AF:
0.194
AC:
1006
AN:
5182
South Asian (SAS)
AF:
0.212
AC:
1021
AN:
4824
European-Finnish (FIN)
AF:
0.157
AC:
1664
AN:
10584
Middle Eastern (MID)
AF:
0.201
AC:
59
AN:
294
European-Non Finnish (NFE)
AF:
0.171
AC:
11621
AN:
67988
Other (OTH)
AF:
0.172
AC:
364
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
985
1970
2955
3940
4925
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
256
512
768
1024
1280
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.145
Hom.:
943
Bravo
AF:
0.148
EpiCase
AF:
0.173
EpiControl
AF:
0.170

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.66
CADD
Benign
2.9
DANN
Benign
0.68
PhyloP100
-0.57
Mutation Taster
=86/14
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12428661; hg19: chr13-99575568; COSMIC: COSV59623639; API