X-11254716-CAAAAAAAAAAAA-CA

Variant names:

• chrX-11254716-CAAAAAAAAAAA-C
• rs751080433
• NM_013427.3:c.589-20_589-10delTTTTTTTTTTT

Variant summary

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

The NM_013427.3(ARHGAP6):​c.589-20_589-10delTTTTTTTTTTT variant causes a intron change. The variant allele was found at a frequency of 0.0000012 in 833,798 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0000012 (0 hom. 0 hem.)
• Consequence: ARHGAP6 NM_013427.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.92
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP6	NM_013427.3	MANE Select	c.589-20_589-10delTTTTTTTTTTT		intron	N/A	NP_038286.2	O43182-1
	ARHGAP6	NM_001287242.2		c.49-20_49-10delTTTTTTTTTTT		intron	N/A	NP_001274171.1
	ARHGAP6	NM_013423.3		c.-21-20_-21-10delTTTTTTTTTTT		intron	N/A	NP_038267.1	O43182-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP6	ENST00000337414.9	TSL:1 MANE Select	c.589-20_589-10delTTTTTTTTTTT		intron	N/A	ENSP00000338967.4	O43182-1
	ARHGAP6	ENST00000303025.10	TSL:1	c.-21-20_-21-10delTTTTTTTTTTT		intron	N/A	ENSP00000302312.6	O43182-4
	ARHGAP6	ENST00000380736.5	TSL:1	c.-21-20_-21-10delTTTTTTTTTTT		intron	N/A	ENSP00000370112.1	O43182-4

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome AF: 0.00000120 AC: 1 AN: 833798 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 242246

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 18946

American (AMR) AF: 0.00 AC: 0 AN: 10368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11140

East Asian (EAS) AF: 0.00 AC: 0 AN: 21878

South Asian (SAS) AF: 0.00 AC: 0 AN: 19493

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22017

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2016

European-Non Finnish (NFE) AF: 0.00000144 AC: 1 AN: 693570

Other (OTH) AF: 0.00 AC: 0 AN: 34370

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs751080433; hg19: chrX-11272836;