chr2-38954448-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001145451.5(ARHGEF33):c.1213C>T(p.His405Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000717 in 1,548,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00037 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000039 ( 0 hom. )
Consequence
ARHGEF33
NM_001145451.5 missense
NM_001145451.5 missense
Scores
1
5
10
Clinical Significance
Conservation
PhyloP100: 4.52
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]
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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=0.20680118).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARHGEF33 | NM_001145451.5 | c.1213C>T | p.His405Tyr | missense_variant | 13/18 | ENST00000409978.7 | |
ARHGEF33 | NM_001367623.3 | c.1213C>T | p.His405Tyr | missense_variant | 13/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGEF33 | ENST00000409978.7 | c.1213C>T | p.His405Tyr | missense_variant | 13/18 | 5 | NM_001145451.5 | P1 | |
ARHGEF33 | ENST00000698009.1 | c.1357C>T | p.His453Tyr | missense_variant | 14/19 | ||||
ARHGEF33 | ENST00000398800.8 | c.1213C>T | p.His405Tyr | missense_variant | 11/16 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000374 AC: 57AN: 152204Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000640 AC: 10AN: 156276Hom.: 0 AF XY: 0.0000241 AC XY: 2AN XY: 82834
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GnomAD4 exome AF: 0.0000387 AC: 54AN: 1395962Hom.: 0 Cov.: 29 AF XY: 0.0000232 AC XY: 16AN XY: 688776
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GnomAD4 genome ? AF: 0.000374 AC: 57AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.000390 AC XY: 29AN XY: 74360
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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 | Oct 20, 2021 | The c.1213C>T (p.H405Y) alteration is located in exon 11 (coding exon 11) of the ARHGEF33 gene. This alteration results from a C to T substitution at nucleotide position 1213, causing the histidine (H) at amino acid position 405 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Vest4
MVP
ClinPred
T
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at