chrX-131081798-C-T

Variant names:

• chrX-131081798-C-T
• rs878929394
• ENST00000639280.1:c.-276C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000639280.1(ARHGAP36):​c.-276C>T 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 0.000000911 in 1,098,242 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: ARHGAP36 ENST00000639280.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11026776).

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.133C>T	p.Arg45Cys	missense	Exon 2 of 12	NP_659404.2
	ARHGAP36	NM_001282607.2		c.97C>T	p.Arg33Cys	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.-276C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 12	ENSP00000492307.1	Q6ZRI8-3
	ARHGAP36	ENST00000276211.10	TSL:2 MANE Select	c.133C>T	p.Arg45Cys	missense	Exon 2 of 12	ENSP00000276211.5	Q6ZRI8-1
	ARHGAP36	ENST00000370922.5	TSL:1	c.97C>T	p.Arg33Cys	missense	Exon 2 of 12	ENSP00000359960.1	Q6ZRI8-4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098242 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 1 AN XY: 363598

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

American (AMR) AF: 0.00 AC: 0 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: 0.0000185 AC: 1 AN: 54146

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

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842139

Other (OTH) AF: 0.00 AC: 0 AN: 46097

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.015
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.033
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.15
MutPred		0.41		Loss of disorder (P = 0.0116)
MVP		0.043
MPC		1.4
ClinPred		0.96	D
GERP RS		0.12
Varity_R		0.14
gMVP		0.28
Mutation Taster		=96/4	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: rs878929394; hg19: chrX-130215772; COSMIC: COSV99358367; COSMIC: COSV99358367;