chrX-11254716-CAA-C

Position:

• chrX-11254716-CAA-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_013427.3(ARHGAP6):​c.589-11_589-10delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0487 in 725,635 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00048 (0 hom., 0 hem., cov: 19)
  • Exomes 𝑓: 0.051 (0 hom. 0 hem.)
• Consequence: ARHGAP6 NM_013427.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

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]

ARHGAP6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP6	NM_013427.3	c.589-11_589-10delTT		intron_variant		ENST00000337414.9	NP_038286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP6	ENST00000337414.9	c.589-11_589-10delTT		intron_variant		1	NM_013427.3	ENSP00000338967.4

Frequencies

GnomAD3 genomes AF: 0.000481 AC: 17 AN: 35310 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 5874

Gnomad AFR AF: 0.000216

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000608

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00914

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000164

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.108 AC: 1624 AN: 15013 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 991

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.132

Gnomad ASJ exome AF: 0.108

Gnomad EAS exome AF: 0.112

Gnomad SAS exome AF: 0.126

Gnomad FIN exome AF: 0.0149

Gnomad NFE exome AF: 0.126

Gnomad OTH exome AF: 0.125

GnomAD4 exome AF: 0.0511 AC: 35298 AN: 690329 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 181603

Gnomad4 AFR exome AF: 0.0621

Gnomad4 AMR exome AF: 0.0743

Gnomad4 ASJ exome AF: 0.0572

Gnomad4 EAS exome AF: 0.0675

Gnomad4 SAS exome AF: 0.0443

Gnomad4 FIN exome AF: 0.0560

Gnomad4 NFE exome AF: 0.0497

Gnomad4 OTH exome AF: 0.0559

GnomAD4 genome AF: 0.000482 AC: 17 AN: 35306 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 5876

Gnomad4 AFR AF: 0.000216

Gnomad4 AMR AF: 0.000608

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00914

Gnomad4 NFE AF: 0.000164

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs751080433; hg19: chrX-11272836;