rs751080433

chrX-11254716-CAAAAAAAAAAAA-CchrX-11254716-CAAAAAAAAAAAA-CAAAchrX-11254716-CAAAAAAAAAAAA-CAAAAAchrX-11254716-CAAAAAAAAAAAA-CAAAAAAchrX-11254716-CAAAAAAAAAAAA-CAAAAAAAchrX-11254716-CAAAAAAAAAAAA-CAAAAAAAAchrX-11254716-CAAAAAAAAAAAA-CAAAAAAAAAchrX-11254716-CAAAAAAAAAAAA-CAAAAAAAAAAchrX-11254716-CAAAAAAAAAAAA-CAAAAAAAAAAAchrX-11254716-CAAAAAAAAAAAA-CAAAAAAAAAAAAAchrX-11254716-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAchrX-11254716-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAchrX-11254716-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAchrX-11254716-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAchrX-11254716-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAchrX-11254716-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAAAchrX-11254716-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013427.3(ARHGAP6):c.589-21_589-10del variant causes a splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.00000345 in 869,131 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000028 (0 hom., 0 hem., cov: 19)
  • Exomes 𝑓: 0.0000024 (0 hom. 1 hem.)
• Consequence: ARHGAP6 NM_013427.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.92

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP6	NM_013427.3	c.589-21_589-10del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000337414.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP6	ENST00000337414.9	c.589-21_589-10del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_013427.3	P2

Frequencies

GnomAD3 genomes AF: 0.0000283 AC: 1 AN: 35325 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 5877

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000548

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000240 AC: 2 AN: 833806 Hom.: 0 AF XY: 0.00000413 AC XY: 1 AN XY: 242252

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000288

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000283 AC: 1 AN: 35325 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 5877

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000548

Gnomad4 OTH AF: 0.00

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;