rs34274521
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2
The NM_004840.3(ARHGEF6):c.942C>T(p.His314=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000165 in 1,209,690 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 65 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00015 ( 0 hom., 5 hem., cov: 22)
Exomes 𝑓: 0.00017 ( 0 hom. 60 hem. )
Consequence
ARHGEF6
NM_004840.3 synonymous
NM_004840.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.93
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 -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP7
?
Synonymous conserved (PhyloP=1.93 with no splicing effect.
BS2
?
High Hemizygotes in GnomAd4 at 5 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARHGEF6 | NM_004840.3 | c.942C>T | p.His314= | synonymous_variant | 9/22 | ENST00000250617.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGEF6 | ENST00000250617.7 | c.942C>T | p.His314= | synonymous_variant | 9/22 | 1 | NM_004840.3 | P1 | |
ARHGEF6 | ENST00000370622.5 | c.480C>T | p.His160= | synonymous_variant | 8/21 | 1 | |||
ARHGEF6 | ENST00000370620.5 | c.480C>T | p.His160= | synonymous_variant | 8/21 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000151 AC: 17AN: 112400Hom.: 0 Cov.: 22 AF XY: 0.000145 AC XY: 5AN XY: 34558
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GnomAD3 exomes AF: 0.000180 AC: 33AN: 183222Hom.: 0 AF XY: 0.000118 AC XY: 8AN XY: 67718
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GnomAD4 exome AF: 0.000167 AC: 183AN: 1097290Hom.: 0 Cov.: 30 AF XY: 0.000165 AC XY: 60AN XY: 362700
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GnomAD4 genome ? AF: 0.000151 AC: 17AN: 112400Hom.: 0 Cov.: 22 AF XY: 0.000145 AC XY: 5AN XY: 34558
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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 | Genetic Services Laboratory, University of Chicago | Jun 23, 2015 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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