X-131081832-C-G
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_144967.4(ARHGAP36):āc.167C>Gā(p.Ser56Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000911 in 1,098,214 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 23)
Exomes š: 0.0000091 ( 0 hom. 4 hem. )
Consequence
ARHGAP36
NM_144967.4 missense
NM_144967.4 missense
Scores
2
6
9
Clinical Significance
Conservation
PhyloP100: 3.46
Genes affected
ARHGAP36 (HGNC:26388): (Rho GTPase activating protein 36) Predicted to enable GTPase activator activity. Predicted to be involved in regulation of catalytic activity and signal transduction. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.40776488).
BS2
High Hemizygotes in GnomAdExome4 at 4 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARHGAP36 | NM_144967.4 | c.167C>G | p.Ser56Cys | missense_variant | 2/12 | ENST00000276211.10 | |
ARHGAP36 | NM_001282607.2 | c.131C>G | p.Ser44Cys | missense_variant | 2/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGAP36 | ENST00000276211.10 | c.167C>G | p.Ser56Cys | missense_variant | 2/12 | 2 | NM_144967.4 | P4 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
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23
GnomAD3 exomes AF: 0.0000109 AC: 2AN: 183416Hom.: 0 AF XY: 0.0000147 AC XY: 1AN XY: 67848
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GnomAD4 exome AF: 0.00000911 AC: 10AN: 1098214Hom.: 0 Cov.: 34 AF XY: 0.0000110 AC XY: 4AN XY: 363570
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GnomAD4 genome Cov.: 23
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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 | Nov 17, 2022 | The c.167C>G (p.S56C) alteration is located in exon 2 (coding exon 1) of the ARHGAP36 gene. This alteration results from a C to G substitution at nucleotide position 167, causing the serine (S) at amino acid position 56 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Pathogenic
D;D;D;D
Sift4G
Pathogenic
D;D;D;.
Polyphen
D;D;.;D
Vest4
MutPred
Loss of disorder (P = 0.0016);.;.;.;
MVP
MPC
ClinPred
D
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