chrX-131083860-G-A

Variant names:

• chrX-131083860-G-A
• rs146720933
• NM_144967.4:c.446G>A

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.446G>A​(p.Arg149His) variant causes a missense change. The variant allele was found at a frequency of 0.0000429 in 1,210,944 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 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 0.000035 (0 hom., 1 hem., cov: 24)
  • Exomes 𝑓: 0.000044 (0 hom. 9 hem.)
• Consequence: ARHGAP36 NM_144967.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.08
• Publications: 6 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=0.11328629).
• BS2: High Hemizygotes in GnomAdExome4 at 9 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.446G>A	p.Arg149His	missense	Exon 4 of 12	NP_659404.2
	ARHGAP36	NM_001282607.2		c.410G>A	p.Arg137His	missense	Exon 4 of 12	NP_001269536.1	Q6ZRI8-4
	ARHGAP36	NM_001330651.1		c.38G>A	p.Arg13His	missense	Exon 3 of 11	NP_001317580.1	Q6ZRI8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP36	ENST00000276211.10	TSL:2 MANE Select	c.446G>A	p.Arg149His	missense	Exon 4 of 12	ENSP00000276211.5	Q6ZRI8-1
	ARHGAP36	ENST00000370922.5	TSL:1	c.410G>A	p.Arg137His	missense	Exon 4 of 12	ENSP00000359960.1	Q6ZRI8-4
	ARHGAP36	ENST00000412432.6	TSL:1	c.353G>A	p.Arg118His	missense	Exon 4 of 12	ENSP00000408515.2	Q6ZRI8-2

Frequencies

GnomAD3 genomes AF: 0.0000355 AC: 4 AN: 112641 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000750

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000437 AC: 48 AN: 1098250 Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 9 AN XY: 363606

African (AFR) AF: 0.0000379 AC: 1 AN: 26402

American (AMR) AF: 0.00 AC: 0 AN: 35207

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 54148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4129

European-Non Finnish (NFE) AF: 0.0000487 AC: 41 AN: 842146

Other (OTH) AF: 0.000130 AC: 6 AN: 46094

GnomAD4 genome AF: 0.0000355 AC: 4 AN: 112694 Hom.: 0 Cov.: 24 AF XY: 0.0000287 AC XY: 1 AN XY: 34840

African (AFR) AF: 0.00 AC: 0 AN: 31097

American (AMR) AF: 0.00 AC: 0 AN: 10754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2660

East Asian (EAS) AF: 0.00 AC: 0 AN: 3551

South Asian (SAS) AF: 0.00 AC: 0 AN: 2698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6203

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 213

European-Non Finnish (NFE) AF: 0.0000750 AC: 4 AN: 53306

Other (OTH) AF: 0.00 AC: 0 AN: 1523

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.0000416

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.0000330 AC: 4

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	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.14
Sift	Uncertain	0.011	D
Sift4G	Benign	0.071	T
Polyphen		1.0	D
Vest4		0.098
MVP		0.27
MPC		0.74
ClinPred		0.32	T
GERP RS		3.5
PromoterAI		0.019	Neutral
Varity_R		0.11
gMVP		0.49
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs146720933; hg19: chrX-130217834; COSMIC: COSV52264471;