X-131083961-G-T

Variant names:

• chrX-131083961-G-T
• rs1250593683
• NM_144967.4:c.547G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_144967.4(ARHGAP36):​c.547G>T​(p.Gly183Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000165 in 1,208,934 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: ARHGAP36 NM_144967.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.17
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35824877).

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.547G>T	p.Gly183Trp	missense	Exon 4 of 12	NP_659404.2
	ARHGAP36	NM_001282607.2		c.511G>T	p.Gly171Trp	missense	Exon 4 of 12	NP_001269536.1	Q6ZRI8-4
	ARHGAP36	NM_001330651.1		c.139G>T	p.Gly47Trp	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.547G>T	p.Gly183Trp	missense	Exon 4 of 12	ENSP00000276211.5	Q6ZRI8-1
	ARHGAP36	ENST00000370922.5	TSL:1	c.511G>T	p.Gly171Trp	missense	Exon 4 of 12	ENSP00000359960.1	Q6ZRI8-4
	ARHGAP36	ENST00000412432.6	TSL:1	c.454G>T	p.Gly152Trp	missense	Exon 4 of 12	ENSP00000408515.2	Q6ZRI8-2

Frequencies

GnomAD3 genomes AF: 0.00000892 AC: 1 AN: 112159 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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000558 AC: 1 AN: 179103 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000127

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1096775 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 362455

African (AFR) AF: 0.00 AC: 0 AN: 26380

American (AMR) AF: 0.00 AC: 0 AN: 35133

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19358

East Asian (EAS) AF: 0.00 AC: 0 AN: 30182

South Asian (SAS) AF: 0.00 AC: 0 AN: 54035

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40459

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3690

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841535

Other (OTH) AF: 0.00 AC: 0 AN: 46003

GnomAD4 genome AF: 0.00000892 AC: 1 AN: 112159 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34313

African (AFR) AF: 0.00 AC: 0 AN: 30808

American (AMR) AF: 0.00 AC: 0 AN: 10684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2655

East Asian (EAS) AF: 0.00 AC: 0 AN: 3540

South Asian (SAS) AF: 0.00 AC: 0 AN: 2655

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53217

Other (OTH) AF: 0.00 AC: 0 AN: 1501

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Uncertain	0.50
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	T
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.2
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.22
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.044	D
Polyphen		1.0	D
Vest4		0.59
MutPred		0.45		Loss of disorder (P = 0.0096)
MVP		0.37
MPC		1.7
ClinPred		0.94	D
GERP RS		4.2
PromoterAI		0.022	Neutral
Varity_R		0.19
gMVP		0.78
Mutation Taster		=86/14	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: rs1250593683; hg19: chrX-130217935;