chrX-131084303-T-C

Variant names:

• chrX-131084303-T-C
• rs1025193472
• NM_144967.4:c.644T>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_144967.4(ARHGAP36):​c.644T>C​(p.Ile215Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000826 in 1,210,277 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000073 (0 hom. 0 hem.)
• Consequence: ARHGAP36 NM_144967.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.56
• Publications: 1 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.34510276).

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.644T>C	p.Ile215Thr	missense	Exon 5 of 12	NP_659404.2
	ARHGAP36	NM_001282607.2		c.608T>C	p.Ile203Thr	missense	Exon 5 of 12	NP_001269536.1	Q6ZRI8-4
	ARHGAP36	NM_001330651.1		c.236T>C	p.Ile79Thr	missense	Exon 4 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.644T>C	p.Ile215Thr	missense	Exon 5 of 12	ENSP00000276211.5	Q6ZRI8-1
	ARHGAP36	ENST00000370922.5	TSL:1	c.608T>C	p.Ile203Thr	missense	Exon 5 of 12	ENSP00000359960.1	Q6ZRI8-4
	ARHGAP36	ENST00000412432.6	TSL:1	c.551T>C	p.Ile184Thr	missense	Exon 5 of 12	ENSP00000408515.2	Q6ZRI8-2

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112182 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

GnomAD4 exome AF: 0.00000729 AC: 8 AN: 1098095 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363451

African (AFR) AF: 0.00 AC: 0 AN: 26402

American (AMR) AF: 0.00 AC: 0 AN: 35201

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19384

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 54125

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

Middle Eastern (MID) AF: 0.000726 AC: 3 AN: 4133

European-Non Finnish (NFE) AF: 0.00000594 AC: 5 AN: 842021

Other (OTH) AF: 0.00 AC: 0 AN: 46091

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112182 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34360

African (AFR) AF: 0.00 AC: 0 AN: 30811

American (AMR) AF: 0.00 AC: 0 AN: 10704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2654

East Asian (EAS) AF: 0.00 AC: 0 AN: 3554

South Asian (SAS) AF: 0.00 AC: 0 AN: 2669

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6122

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53244

Other (OTH) AF: 0.00 AC: 0 AN: 1505

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.52
DEOGEN2	Benign	0.026	T
FATHMM_MKL	Benign	0.28	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.81	L
PhyloP100		3.6
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.52	N
REVEL	Benign	0.15
Sift	Benign	0.35	T
Sift4G	Benign	0.54	T
Polyphen		0.84	P
Vest4		0.13
MutPred		0.70		Loss of stability (P = 0.0231)
MVP		0.26
MPC		0.87
ClinPred		0.53	D
GERP RS		5.0
Varity_R		0.070
gMVP		0.77
Mutation Taster		=92/8	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: rs1025193472; hg19: chrX-130218277;