NM_013427.3:c.589-73889A>C

Variant names:

• chrX-11328596-T-G
• rs6640729
• NM_013427.3:c.589-73889A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013427.3(ARHGAP6):​c.589-73889A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 111,942 control chromosomes in the GnomAD database, including 1,056 homozygotes. There are 3,380 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: 𝑓 0.093 (1056 hom., 3380 hem., cov: 23)
• Consequence: ARHGAP6 NM_013427.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.728
• Publications: 3 publications found

Genes affected

ARHGAP6 (HGNC:676): (Rho GTPase activating protein 6) This gene encodes a member of the rhoGAP family of proteins which play a role in the regulation of actin polymerization at the plasma membrane during several cellular processes. This protein is thought to have two independent functions, one as a GTPase-activating protein with specificity for RhoA, and another as a cytoskeletal protein that promotes actin remodeling. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013427.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP6	NM_013427.3	MANE Select	c.589-73889A>C		intron	N/A	NP_038286.2
	ARHGAP6	NM_001287242.2		c.49-73889A>C		intron	N/A	NP_001274171.1
	ARHGAP6	NM_006125.3		c.589-73889A>C		intron	N/A	NP_006116.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP6	ENST00000337414.9	TSL:1 MANE Select	c.589-73889A>C		intron	N/A	ENSP00000338967.4
	ARHGAP6	ENST00000380736.5	TSL:1	c.-21-73889A>C		intron	N/A	ENSP00000370112.1
	ARHGAP6	ENST00000380718.1	TSL:1	c.589-73889A>C		intron	N/A	ENSP00000370094.1

Frequencies

GnomAD3 genomes AF: 0.0928 AC: 10387 AN: 111889 Hom.: 1050 Cov.: 23

Gnomad AFR AF: 0.0202

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.0332

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.0954

Gnomad FIN AF: 0.0710

Gnomad MID AF: 0.0588

Gnomad NFE AF: 0.0546

Gnomad OTH AF: 0.119

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0929 AC: 10398 AN: 111942 Hom.: 1056 Cov.: 23 AF XY: 0.0990 AC XY: 3380 AN XY: 34128

African (AFR) AF: 0.0201 AC: 624 AN: 30984

American (AMR) AF: 0.386 AC: 4027 AN: 10434

Ashkenazi Jewish (ASJ) AF: 0.0332 AC: 88 AN: 2654

East Asian (EAS) AF: 0.529 AC: 1854 AN: 3502

South Asian (SAS) AF: 0.0945 AC: 252 AN: 2666

European-Finnish (FIN) AF: 0.0710 AC: 433 AN: 6100

Middle Eastern (MID) AF: 0.0642 AC: 14 AN: 218

European-Non Finnish (NFE) AF: 0.0546 AC: 2902 AN: 53176

Other (OTH) AF: 0.118 AC: 180 AN: 1525

Alfa AF: 0.0853 Hom.: 6071

Bravo AF: 0.125

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.2
DANN	Benign	0.76
PhyloP100		0.73
Mutation Taster		=100/0	polymorphism (auto)

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: rs6640729; hg19: chrX-11346716;