X-131084258-C-A

Position:

• chrX-131084258-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144967.4(ARHGAP36):​c.599C>A​(p.Ala200Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A200V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: ARHGAP36 NM_144967.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.15

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP36	NM_144967.4	c.599C>A	p.Ala200Asp	missense_variant	5/12	ENST00000276211.10
ARHGAP36	NM_001282607.2	c.563C>A	p.Ala188Asp	missense_variant	5/12
ARHGAP36	NM_001330651.1	c.191C>A	p.Ala64Asp	missense_variant	4/11
ARHGAP36	XM_011531280.2	c.191C>A	p.Ala64Asp	missense_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP36	ENST00000276211.10	c.599C>A	p.Ala200Asp	missense_variant	5/12	2	NM_144967.4	P4

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1096377 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 361925

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2022

The c.599C>A (p.A200D) alteration is located in exon 5 (coding exon 4) of the ARHGAP36 gene. This alteration results from a C to A substitution at nucleotide position 599, causing the alanine (A) at amino acid position 200 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.057	T;.;.;.;.;.
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.61	T;T;T;T;T;.
M_CAP	Benign	0.0091	T
MetaRNN	Uncertain	0.48	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	M;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.5	N;N;N;.;N;N
REVEL	Benign	0.19
Sift	Benign	0.093	T;T;D;.;T;T
Sift4G	Uncertain	0.016	D;D;D;.;.;D
Polyphen		1.0	D;D;.;.;D;.
Vest4		0.17
MutPred		0.69		Gain of relative solvent accessibility (P = 0.0479);.;.;.;.;.;
MVP		0.19
MPC		0.89
ClinPred		0.62	D
GERP RS		5.0
Varity_R		0.24
gMVP		0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-130218232;