GeneBe

rs386389985

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001145451.5(ARHGEF33):​c.2343+2216_2343+2226delAAAAAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 0)

Consequence

ARHGEF33
NM_001145451.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.445

Publications

1 publications found
Variant links:
Genes affected
ARHGEF33 (HGNC:37252): (Rho guanine nucleotide exchange factor 33) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. [provided by Alliance of Genome Resources, Apr 2022]
SOS1 (HGNC:11187): (SOS Ras/Rac guanine nucleotide exchange factor 1) This gene encodes a protein that is a guanine nucleotide exchange factor for RAS proteins, membrane proteins that bind guanine nucleotides and participate in signal transduction pathways. GTP binding activates and GTP hydrolysis inactivates RAS proteins. The product of this gene may regulate RAS proteins by facilitating the exchange of GTP for GDP. Mutations in this gene are associated with gingival fibromatosis 1 and Noonan syndrome type 4. [provided by RefSeq, Jul 2008]
SOS1 Gene-Disease associations (from GenCC):
  • Noonan syndrome
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
  • Noonan syndrome 4
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Genomics England PanelApp
  • fibromatosis, gingival, 1
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • hereditary gingival fibromatosis
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • cardiofaciocutaneous syndrome
    Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
  • Costello syndrome
    Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
  • Noonan syndrome with multiple lentigines
    Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
  • Noonan syndrome-like disorder with loose anagen hair
    Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145451.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ARHGEF33
NM_001145451.5
MANE Select
c.2343+2216_2343+2226delAAAAAAAAAAA
intron
N/ANP_001138923.2A8MVX0-2
ARHGEF33
NM_001367623.3
c.2343+2216_2343+2226delAAAAAAAAAAA
intron
N/ANP_001354552.1A8MVX0-1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ARHGEF33
ENST00000409978.7
TSL:5 MANE Select
c.2343+2202_2343+2212delAAAAAAAAAAA
intron
N/AENSP00000387020.1A8MVX0-2
SOS1
ENST00000692089.1
c.3400-15_3400-5delTTTTTTTTTTT
splice_region intron
N/AENSP00000508626.1A0A8I5QJ77
ARHGEF33
ENST00000698009.1
c.2487+2202_2487+2212delAAAAAAAAAAA
intron
N/AENSP00000513494.1A0A8V8TLC5

Frequencies

GnomAD3 genomes
AF:
0.0000534
AC:
3
AN:
56132
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.000166
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000604
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0000535
AC:
3
AN:
56124
Hom.:
0
Cov.:
0
AF XY:
0.000123
AC XY:
3
AN XY:
24330
show subpopulations
African (AFR)
AF:
0.000165
AC:
2
AN:
12110
American (AMR)
AF:
0.00
AC:
0
AN:
3198
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
1960
East Asian (EAS)
AF:
0.000609
AC:
1
AN:
1642
South Asian (SAS)
AF:
0.00
AC:
0
AN:
1172
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
414
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
40
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
34452
Other (OTH)
AF:
0.00
AC:
0
AN:
646
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.708
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

Genome 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
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.45

Splicing

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

Publications

Other links and lift over

dbSNP: rs386389985; hg19: chr2-39189990; API