chrX-11254716-CAAAAA-C

Position:

• chrX-11254716-CAAAAA-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_013427.3(ARHGAP6):​c.589-14_589-10delTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 858,010 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., 9 hem., cov: 19)
  • Exomes 𝑓: 0.0013 (0 hom. 8 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Hemizygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP6	NM_013427.3	c.589-14_589-10delTTTTT		intron_variant		ENST00000337414.9	NP_038286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP6	ENST00000337414.9	c.589-14_589-10delTTTTT		intron_variant		1	NM_013427.3	ENSP00000338967.4

Frequencies

GnomAD3 genomes AF: 0.00108 AC: 38 AN: 35322 Hom.: 0 Cov.: 19 AF XY: 0.00153 AC XY: 9 AN XY: 5876

Gnomad AFR AF: 0.000108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00304

Gnomad ASJ AF: 0.0189

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000383

Gnomad OTH AF: 0.00438

GnomAD3 exomes AF: 0.0171 AC: 257 AN: 15013 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 991

Gnomad AFR exome AF: 0.0167

Gnomad AMR exome AF: 0.0147

Gnomad ASJ exome AF: 0.0297

Gnomad EAS exome AF: 0.0177

Gnomad SAS exome AF: 0.0241

Gnomad FIN exome AF: 0.00361

Gnomad NFE exome AF: 0.0200

Gnomad OTH exome AF: 0.0260

GnomAD4 exome AF: 0.00130 AC: 1071 AN: 822692 Hom.: 0 AF XY: 0.0000338 AC XY: 8 AN XY: 236940

Gnomad4 AFR exome AF: 0.00193

Gnomad4 AMR exome AF: 0.00566

Gnomad4 ASJ exome AF: 0.00688

Gnomad4 EAS exome AF: 0.00181

Gnomad4 SAS exome AF: 0.00288

Gnomad4 FIN exome AF: 0.00194

Gnomad4 NFE exome AF: 0.00101

Gnomad4 OTH exome AF: 0.00203

GnomAD4 genome AF: 0.00108 AC: 38 AN: 35318 Hom.: 0 Cov.: 19 AF XY: 0.00153 AC XY: 9 AN XY: 5878

Gnomad4 AFR AF: 0.000108

Gnomad4 AMR AF: 0.00304

Gnomad4 ASJ AF: 0.0189

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000383

Gnomad4 OTH AF: 0.00429

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;