rs774734407
Positions:
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2
The NM_004840.3(ARHGEF6):c.1685C>T(p.Ser562Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000438 in 1,210,171 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., 2 hem., cov: 23)
Exomes 𝑓: 0.000043 ( 0 hom. 17 hem. )
Consequence
ARHGEF6
NM_004840.3 missense
NM_004840.3 missense
Scores
1
13
Clinical Significance
Conservation
PhyloP100: 3.78
Genes affected
ARHGEF6 (HGNC:685): (Rac/Cdc42 guanine nucleotide exchange factor 6) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein belongs to a family of cytoplasmic proteins that activate the Ras-like family of Rho proteins by exchanging bound GDP for GTP. It may form a complex with G proteins and stimulate Rho-dependent signals. This protein is activated by PI3-kinase. Mutations in this gene can cause X-chromosomal non-specific cognitive disability. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.1420719).
BP6
?
Variant X-136680750-G-A is Benign according to our data. Variant chrX-136680750-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 434301.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Hemizygotes in GnomAd4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARHGEF6 | NM_004840.3 | c.1685C>T | p.Ser562Leu | missense_variant | 15/22 | ENST00000250617.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGEF6 | ENST00000250617.7 | c.1685C>T | p.Ser562Leu | missense_variant | 15/22 | 1 | NM_004840.3 | P1 | |
ARHGEF6 | ENST00000370622.5 | c.1223C>T | p.Ser408Leu | missense_variant | 14/21 | 1 | |||
ARHGEF6 | ENST00000370620.5 | c.1223C>T | p.Ser408Leu | missense_variant | 14/21 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000535 AC: 6AN: 112222Hom.: 0 Cov.: 23 AF XY: 0.0000582 AC XY: 2AN XY: 34370
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GnomAD3 exomes AF: 0.0000600 AC: 11AN: 183430Hom.: 0 AF XY: 0.0000737 AC XY: 5AN XY: 67868
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GnomAD4 exome AF: 0.0000428 AC: 47AN: 1097949Hom.: 0 Cov.: 30 AF XY: 0.0000468 AC XY: 17AN XY: 363333
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GnomAD4 genome ? AF: 0.0000535 AC: 6AN: 112222Hom.: 0 Cov.: 23 AF XY: 0.0000582 AC XY: 2AN XY: 34370
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 05, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
FATHMM_MKL
Benign
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
0.0010
.;.;B
Vest4
MutPred
0.24
.;.;Loss of phosphorylation at S562 (P = 0.0028);
MVP
MPC
0.25
ClinPred
T
GERP RS
Varity_R
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