rs773226775

Variant names:

• chrX-131081791-C-A
• rs773226775
• NM_144967.4:c.126C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-131081791-C-A
• chrX-131081791-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_144967.4(ARHGAP36):​c.126C>A​(p.Asn42Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000454 in 1,210,503 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 20 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 0.000045 (0 hom. 18 hem.)
• Consequence: ARHGAP36 NM_144967.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.291
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07016283).
• BS2: High Hemizygotes in GnomAd4 at 2 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144967.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP36	NM_144967.4	MANE Select	c.126C>A	p.Asn42Lys	missense	Exon 2 of 12	NP_659404.2
	ARHGAP36	NM_001282607.2		c.90C>A	p.Asn30Lys	missense	Exon 2 of 12	NP_001269536.1	Q6ZRI8-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP36	ENST00000276211.10	TSL:2 MANE Select	c.126C>A	p.Asn42Lys	missense	Exon 2 of 12	ENSP00000276211.5	Q6ZRI8-1
	ARHGAP36	ENST00000370922.5	TSL:1	c.90C>A	p.Asn30Lys	missense	Exon 2 of 12	ENSP00000359960.1	Q6ZRI8-4
	ARHGAP36	ENST00000412432.6	TSL:1	c.33C>A	p.Asn11Lys	missense	Exon 2 of 12	ENSP00000408515.2	Q6ZRI8-2

Frequencies

GnomAD3 genomes AF: 0.0000535 AC: 6 AN: 112210 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000188

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000563

Gnomad OTH AF: 0.000670

GnomAD2 exomes AF: 0.0000763 AC: 14 AN: 183472 AF XY: 0.0000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000109

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000854

Gnomad OTH exome AF: 0.000662

GnomAD4 exome AF: 0.0000446 AC: 49 AN: 1098241 Hom.: 0 Cov.: 34 AF XY: 0.0000495 AC XY: 18 AN XY: 363595

African (AFR) AF: 0.000114 AC: 3 AN: 26402

American (AMR) AF: 0.000170 AC: 6 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.0000554 AC: 3 AN: 54145

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40533

Middle Eastern (MID) AF: 0.000726 AC: 3 AN: 4131

European-Non Finnish (NFE) AF: 0.0000356 AC: 30 AN: 842135

Other (OTH) AF: 0.0000868 AC: 4 AN: 46097

GnomAD4 genome AF: 0.0000534 AC: 6 AN: 112262 Hom.: 0 Cov.: 23 AF XY: 0.0000581 AC XY: 2 AN XY: 34452

African (AFR) AF: 0.00 AC: 0 AN: 30903

American (AMR) AF: 0.000187 AC: 2 AN: 10676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3550

South Asian (SAS) AF: 0.00 AC: 0 AN: 2662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6158

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.0000563 AC: 3 AN: 53245

Other (OTH) AF: 0.000661 AC: 1 AN: 1512

Alfa AF: 0.0000540 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000906 AC: 11

EpiCase AF: 0.000273

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.9
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.29
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.046
Sift	Benign	0.080	T
Sift4G	Benign	0.36	T
Polyphen		0.76	P
Vest4		0.15
MutPred		0.28		Gain of methylation at N42 (P = 0.0062)
MVP		0.13
MPC		1.1
ClinPred		0.035	T
GERP RS		1.3
Varity_R		0.068
gMVP		0.28
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs773226775; hg19: chrX-130215765;