chrX-11254716-CAAAAAA-C

Variant names:

• chrX-11254716-CAAAAAA-C
• rs751080433
• NM_013427.3:c.589-15_589-10delTTTTTT

Variant summary

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

The NM_013427.3(ARHGAP6):​c.589-15_589-10delTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000325 in 830,607 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: 𝑓 0.0 (0 hom., 0 hem., cov: 19)
  • Exomes 𝑓: 0.00033 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: ARHGAP6 NM_013427.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131
• 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.589-15_589-10delTTTTTT		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.589-15_589-10delTTTTTT		intron_variant	Intron 1 of 12	1	NM_013427.3	ENSP00000338967.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 35325 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.00

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: 0.00

GnomAD4 exome AF: 0.000325 AC: 270 AN: 830607 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 240389

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

African (AFR) AF: 0.000688 AC: 13 AN: 18889

American (AMR) AF: 0.00136 AC: 14 AN: 10262

Ashkenazi Jewish (ASJ) AF: 0.00163 AC: 18 AN: 11064

East Asian (EAS) AF: 0.000597 AC: 13 AN: 21786

South Asian (SAS) AF: 0.00114 AC: 22 AN: 19328

European-Finnish (FIN) AF: 0.000365 AC: 8 AN: 21917

Middle Eastern (MID) AF: 0.00100 AC: 2 AN: 1995

European-Non Finnish (NFE) AF: 0.000237 AC: 164 AN: 691127

Other (OTH) AF: 0.000467 AC: 16 AN: 34239

⚠️ 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 35325 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 5877

African (AFR) AF: 0.00 AC: 0 AN: 9248

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: 18262

Other (OTH) AF: 0.00 AC: 0 AN: 457

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.13
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;