chrX-11254716-CAAAAAAAAAA-C

Variant names:

• chrX-11254716-CAAAAAAAAAA-C
• rs751080433
• NM_013427.3:c.589-19_589-10delTTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_013427.3(ARHGAP6):​c.589-19_589-10delTTTTTTTTTT variant causes a intron change. The variant allele was found at a frequency of 0.0000036 in 833,782 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: not found (cov: 19)
  • Exomes 𝑓: 0.0000036 (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 2 ACMG points.

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

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.589-19_589-10delTTTTTTTTTT		intron	N/A	NP_038286.2
	ARHGAP6	NM_001287242.2		c.49-19_49-10delTTTTTTTTTT		intron	N/A	NP_001274171.1
	ARHGAP6	NM_013423.3		c.-21-19_-21-10delTTTTTTTTTT		intron	N/A	NP_038267.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP6	ENST00000337414.9	TSL:1 MANE Select	c.589-19_589-10delTTTTTTTTTT		intron	N/A	ENSP00000338967.4
	ARHGAP6	ENST00000303025.10	TSL:1	c.-21-19_-21-10delTTTTTTTTTT		intron	N/A	ENSP00000302312.6
	ARHGAP6	ENST00000380736.5	TSL:1	c.-21-19_-21-10delTTTTTTTTTT		intron	N/A	ENSP00000370112.1

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome AF: 0.00000360 AC: 3 AN: 833782 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 242234

⚠️ 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: 10370

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 21879

South Asian (SAS) AF: 0.0000513 AC: 1 AN: 19492

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: 0.00000288 AC: 2 AN: 693553

Other (OTH) AF: 0.00 AC: 0 AN: 34369

⚠️ 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;