ENST00000639280.1:c.-242C>G

Variant names:

• chrX-131081832-C-G
• rs1435847344
• ENST00000639280.1:c.-242C>G

Variant summary

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

The ENST00000639280.1(ARHGAP36):​c.-242C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000911 in 1,098,214 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000091 (0 hom. 4 hem.)
• Consequence: ARHGAP36 ENST00000639280.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.46
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.40776488).
• BS2: High Hemizygotes in GnomAdExome4 at 4 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000639280.1. 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.167C>G	p.Ser56Cys	missense	Exon 2 of 12	NP_659404.2
	ARHGAP36	NM_001282607.2		c.131C>G	p.Ser44Cys	missense	Exon 2 of 12	NP_001269536.1	Q6ZRI8-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP36	ENST00000639280.1	TSL:1	c.-242C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 12	ENSP00000492307.1	Q6ZRI8-3
	ARHGAP36	ENST00000276211.10	TSL:2 MANE Select	c.167C>G	p.Ser56Cys	missense	Exon 2 of 12	ENSP00000276211.5	Q6ZRI8-1
	ARHGAP36	ENST00000370922.5	TSL:1	c.131C>G	p.Ser44Cys	missense	Exon 2 of 12	ENSP00000359960.1	Q6ZRI8-4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000109 AC: 2 AN: 183416 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.00000911 AC: 10 AN: 1098214 Hom.: 0 Cov.: 34 AF XY: 0.0000110 AC XY: 4 AN XY: 363570

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

American (AMR) AF: 0.0000568 AC: 2 AN: 35204

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: 54149

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40530

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

European-Non Finnish (NFE) AF: 0.00000237 AC: 2 AN: 842112

Other (OTH) AF: 0.000130 AC: 6 AN: 46096

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000567

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	0.49
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.5
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.48
MutPred		0.59		Loss of disorder (P = 0.0016)
MVP		0.24
MPC		1.6
ClinPred		0.97	D
GERP RS		3.3
Varity_R		0.53
gMVP		0.44
Mutation Taster		=64/36	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: rs1435847344; hg19: chrX-130215806;