NM_144967.4:c.884A>G

Variant names:

• chrX-131084993-A-G
• rs140912896
• NM_144967.4:c.884A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_144967.4(ARHGAP36):​c.884A>G​(p.Lys295Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000405 in 1,210,069 control chromosomes in the GnomAD database, including 1 homozygotes. There are 18 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 0.000018 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000043 (1 hom. 17 hem.)
• Consequence: ARHGAP36 NM_144967.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 3.68
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2961262).
• BS2: High Hemizygotes in GnomAdExome4 at 17 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.884A>G	p.Lys295Arg	missense	Exon 7 of 12	NP_659404.2
	ARHGAP36	NM_001282607.2		c.848A>G	p.Lys283Arg	missense	Exon 7 of 12	NP_001269536.1	Q6ZRI8-4
	ARHGAP36	NM_001330651.1		c.476A>G	p.Lys159Arg	missense	Exon 6 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.884A>G	p.Lys295Arg	missense	Exon 7 of 12	ENSP00000276211.5	Q6ZRI8-1
	ARHGAP36	ENST00000370922.5	TSL:1	c.848A>G	p.Lys283Arg	missense	Exon 7 of 12	ENSP00000359960.1	Q6ZRI8-4
	ARHGAP36	ENST00000412432.6	TSL:1	c.791A>G	p.Lys264Arg	missense	Exon 7 of 12	ENSP00000408515.2	Q6ZRI8-2

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 111942 Hom.: 0 Cov.: 23

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: 0.0000376

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000382 AC: 7 AN: 183227 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000134

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000188

Gnomad NFE exome AF: 0.0000367

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000428 AC: 47 AN: 1098127 Hom.: 1 Cov.: 32 AF XY: 0.0000468 AC XY: 17 AN XY: 363483

African (AFR) AF: 0.00 AC: 0 AN: 26399

American (AMR) AF: 0.00 AC: 0 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.0000516 AC: 1 AN: 19384

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 54141

European-Finnish (FIN) AF: 0.000247 AC: 10 AN: 40489

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.0000404 AC: 34 AN: 842082

Other (OTH) AF: 0.0000434 AC: 2 AN: 46091

GnomAD4 genome AF: 0.0000179 AC: 2 AN: 111942 Hom.: 0 Cov.: 23 AF XY: 0.0000293 AC XY: 1 AN XY: 34082

African (AFR) AF: 0.00 AC: 0 AN: 30754

American (AMR) AF: 0.00 AC: 0 AN: 10623

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3553

South Asian (SAS) AF: 0.00 AC: 0 AN: 2646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6105

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53178

Other (OTH) AF: 0.00 AC: 0 AN: 1512

Alfa AF: 0.0000953 Hom.: 5

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000297 AC: 2

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.12
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.7
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.38
Sift	Benign	0.032	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.89	P
Vest4		0.32
MVP		0.83
MPC		0.50
ClinPred		0.33	T
GERP RS		4.1
Varity_R		0.28
gMVP		0.92
Mutation Taster		=45/55	disease causing

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: rs140912896; hg19: chrX-130218967;