chrX-11254716-C-CAAAAA

Variant names:

• chrX-11254716-C-CAAAAA
• rs751080433
• NM_013427.3:c.589-14_589-10dupTTTTT

Variant summary

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

The NM_013427.3(ARHGAP6):​c.589-14_589-10dupTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., 0 hem., cov: 19)
  • Exomes 𝑓: 0.0000036 (0 hom. 0 hem.)
• Consequence: ARHGAP6 NM_013427.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP6	NM_013427.3	c.589-14_589-10dupTTTTT		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.589-10_589-9insTTTTT		intron_variant	Intron 1 of 12	1	NM_013427.3	ENSP00000338967.4

Frequencies

GnomAD3 genomes AF: 0.0000849 AC: 3 AN: 35321 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.000216

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: 0.00

Gnomad OTH AF: 0.00219

GnomAD4 exome AF: 0.00000360 AC: 3 AN: 833758 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 242210

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: 21880

South Asian (SAS) AF: 0.00 AC: 0 AN: 19490

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: 0.00000433 AC: 3 AN: 693530

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

GnomAD4 genome AF: 0.0000849 AC: 3 AN: 35321 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 5877

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

African (AFR) AF: 0.000216 AC: 2 AN: 9246

American (AMR) AF: 0.00 AC: 0 AN: 3292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 954

East Asian (EAS) AF: 0.00 AC: 0 AN: 1108

South Asian (SAS) AF: 0.00 AC: 0 AN: 641

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1101

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 68

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 18260

Other (OTH) AF: 0.00219 AC: 1 AN: 457

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000907115), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 45

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.085

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;