X-131086332-C-G

Position:

• chrX-131086332-C-G

Variant summary

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

The NM_144967.4(ARHGAP36):​c.1285C>G​(p.Pro429Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: ARHGAP36 NM_144967.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.17

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.1285C>G	p.Pro429Ala	missense_variant	10/12	ENST00000276211.10
ARHGAP36	NM_001282607.2	c.1249C>G	p.Pro417Ala	missense_variant	10/12
ARHGAP36	NM_001330651.1	c.877C>G	p.Pro293Ala	missense_variant	9/11
ARHGAP36	XM_011531280.2	c.877C>G	p.Pro293Ala	missense_variant	9/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP36	ENST00000276211.10	c.1285C>G	p.Pro429Ala	missense_variant	10/12	2	NM_144967.4	P4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

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

Oct 17, 2023

The c.1285C>G (p.P429A) alteration is located in exon 10 (coding exon 9) of the ARHGAP36 gene. This alteration results from a C to G substitution at nucleotide position 1285, causing the proline (P) at amino acid position 429 to be replaced by an alanine (A). 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	0.26
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T;.;.;.;.
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D;D;D;D;.
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.51	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;.;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-4.0	D;D;.;D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0010	D;D;.;D;D
Sift4G	Uncertain	0.050	T;T;.;.;T
Polyphen		0.97	D;D;.;D;.
Vest4		0.41
MutPred		0.61		Gain of MoRF binding (P = 0.0351);.;.;.;.;
MVP		0.24
MPC		1.5
ClinPred		0.97	D
GERP RS		4.7
Varity_R		0.48
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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-130220306;