GeneBe

17-82032784-CAGG-C

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM1PM2PM4_SupportingPP5

The NM_005052.3(RAC3):​c.186_188delGGA​(p.Glu62del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,788 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RAC3
NM_005052.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.66

Publications

0 publications found
Variant links:
Genes affected
RAC3 (HGNC:9803): (Rac family small GTPase 3) The protein encoded by this gene is a GTPase which belongs to the RAS superfamily of small GTP-binding proteins. Members of this superfamily appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]
RAC3 Gene-Disease associations (from GenCC):
  • neurodevelopmental disorder with structural brain anomalies and dysmorphic facies
    Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM1
In a hotspot region, there are 5 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 5 uncertain in NM_005052.3
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_005052.3. Strenght limited to Supporting due to length of the change: 1aa.
PP5
Variant 17-82032784-CAGG-C is Pathogenic according to our data. Variant chr17-82032784-CAGG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 1723153.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005052.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
RAC3
NM_005052.3
MANE Select
c.186_188delGGAp.Glu62del
disruptive_inframe_deletion
Exon 3 of 6NP_005043.1P60763
RAC3
NM_001316307.2
c.186_188delGGAp.Glu62del
disruptive_inframe_deletion
Exon 3 of 6NP_001303236.1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
RAC3
ENST00000306897.9
TSL:1 MANE Select
c.186_188delGGAp.Glu62del
disruptive_inframe_deletion
Exon 3 of 6ENSP00000304283.4P60763
RAC3
ENST00000924839.1
c.465_467delGGAp.Glu155del
disruptive_inframe_deletion
Exon 3 of 6ENSP00000594898.1
RAC3
ENST00000924841.1
c.186_188delGGAp.Glu62del
disruptive_inframe_deletion
Exon 3 of 6ENSP00000594900.1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460788
Hom.:
0
AF XY:
0.00000138
AC XY:
1
AN XY:
726690
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52374
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111972
Other (OTH)
AF:
0.00
AC:
0
AN:
60380
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
34

ClinVar

ClinVar submissions
Significance:Pathogenic
Revision:no assertion criteria provided
View on ClinVar
Pathogenic
VUS
Benign
Condition
1
-
-
Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
7.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

hg19: chr17-79990660; API