X-11254716-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAA

Variant names:

• chrX-11254716-C-CAAAA
• rs751080433
• NM_013427.3:c.589-13_589-10dupTTTT

Variant summary

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

The NM_013427.3(ARHGAP6):​c.589-13_589-10dupTTTT 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 0.00017 (0 hom., 0 hem., cov: 19)
  • Exomes 𝑓: 0.000022 (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.589-13_589-10dupTTTT		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_589-9insTTTT		intron_variant	Intron 1 of 12	1	NM_013427.3	ENSP00000338967.4

Frequencies

GnomAD3 genomes AF: 0.000170 AC: 6 AN: 35321 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.000541

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: 0.0000216 AC: 18 AN: 833582 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 242114

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

African (AFR) AF: 0.000159 AC: 3 AN: 18919

American (AMR) AF: 0.0000964 AC: 1 AN: 10369

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

East Asian (EAS) AF: 0.0000457 AC: 1 AN: 21880

South Asian (SAS) AF: 0.00 AC: 0 AN: 19487

European-Finnish (FIN) AF: 0.0000454 AC: 1 AN: 22015

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

European-Non Finnish (NFE) AF: 0.0000159 AC: 11 AN: 693392

Other (OTH) AF: 0.0000291 AC: 1 AN: 34365

⚠️ 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 AF: 0.000170 AC: 6 AN: 35317 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 5879

African (AFR) AF: 0.000540 AC: 5 AN: 9256

American (AMR) AF: 0.00 AC: 0 AN: 3290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 1101

South Asian (SAS) AF: 0.00 AC: 0 AN: 634

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 62

European-Non Finnish (NFE) AF: 0.0000548 AC: 1 AN: 18259

Other (OTH) AF: 0.00 AC: 0 AN: 466

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
Mutation Taster		=100/0	polymorphism

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;