X-11254716-CAAAAAAAAAAAA-CAAA

Variant names:

• chrX-11254716-CAAAAAAAAA-C
• rs751080433
• NM_013427.3:c.589-18_589-10delTTTTTTTTT

Variant summary

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

The NM_013427.3(ARHGAP6):​c.589-18_589-10delTTTTTTTTT variant causes a intron change. The variant allele was found at a frequency of 0.0000144 in 833,701 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: 0.000014 (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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP6	NM_013427.3	c.589-18_589-10delTTTTTTTTT		intron_variant	Intron 1 of 12	ENST00000337414.9	NP_038286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP6	ENST00000337414.9	c.589-18_589-10delTTTTTTTTT		intron_variant	Intron 1 of 12	1	NM_013427.3	ENSP00000338967.4

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome AF: 0.0000144 AC: 12 AN: 833701 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 242185

⚠️ 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: 18943

American (AMR) AF: 0.000193 AC: 2 AN: 10367

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11138

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

South Asian (SAS) AF: 0.000103 AC: 2 AN: 19479

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22009

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2015

European-Non Finnish (NFE) AF: 0.0000115 AC: 8 AN: 693506

Other (OTH) AF: 0.00 AC: 0 AN: 34366

⚠️ 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 v4.3

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;