X-11254716-CAAAAAAAAAAAA-CAAAAAAAAAAA

Variant names:

• chrX-11254716-CA-C
• rs751080433
• NM_013427.3:c.589-10delT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_013427.3(ARHGAP6):​c.589-10delT 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 0.017 (1 hom., 31 hem., cov: 19)
  • Exomes 𝑓: 0.20 (0 hom. 14 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0166 (585/35302) while in subpopulation AFR AF = 0.048 (444/9253). AF 95% confidence interval is 0.0443. There are 1 homozygotes in GnomAd4. There are 31 alleles in the male GnomAd4 subpopulation. Median coverage is 19. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 31 gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP6	NM_013427.3	MANE Select	c.589-10delT		intron	N/A	NP_038286.2	O43182-1
	ARHGAP6	NM_001287242.2		c.49-10delT		intron	N/A	NP_001274171.1
	ARHGAP6	NM_013423.3		c.-21-10delT		intron	N/A	NP_038267.1	O43182-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP6	ENST00000337414.9	TSL:1 MANE Select	c.589-10delT		intron	N/A	ENSP00000338967.4	O43182-1
	ARHGAP6	ENST00000303025.10	TSL:1	c.-21-10delT		intron	N/A	ENSP00000302312.6	O43182-4
	ARHGAP6	ENST00000380736.5	TSL:1	c.-21-10delT		intron	N/A	ENSP00000370112.1	O43182-4

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 584 AN: 35306 Hom.: 1 Cov.: 19

Gnomad AFR AF: 0.0479

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00181

Gnomad SAS AF: 0.00312

Gnomad FIN AF: 0.0466

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00257

Gnomad OTH AF: 0.0109

GnomAD2 exomes AF: 0.120 AC: 1803 AN: 15013 AF XY: 0.00

Gnomad AFR exome AF: 0.163

Gnomad AMR exome AF: 0.150

Gnomad ASJ exome AF: 0.161

Gnomad EAS exome AF: 0.156

Gnomad FIN exome AF: 0.0158

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.153

GnomAD4 exome AF: 0.204 AC: 138923 AN: 679391 Hom.: 0 Cov.: 0 AF XY: 0.000114 AC XY: 14 AN XY: 123285

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

African (AFR) AF: 0.211 AC: 3352 AN: 15854

American (AMR) AF: 0.140 AC: 1284 AN: 9184

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 1569 AN: 9147

East Asian (EAS) AF: 0.180 AC: 3342 AN: 18602

South Asian (SAS) AF: 0.157 AC: 2444 AN: 15602

European-Finnish (FIN) AF: 0.133 AC: 2597 AN: 19502

Middle Eastern (MID) AF: 0.165 AC: 261 AN: 1586

European-Non Finnish (NFE) AF: 0.211 AC: 118298 AN: 561470

Other (OTH) AF: 0.203 AC: 5776 AN: 28444

⚠️ 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: 0.0166 AC: 585 AN: 35302 Hom.: 1 Cov.: 19 AF XY: 0.00528 AC XY: 31 AN XY: 5866

African (AFR) AF: 0.0480 AC: 444 AN: 9253

American (AMR) AF: 0.0103 AC: 34 AN: 3290

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

East Asian (EAS) AF: 0.00182 AC: 2 AN: 1101

South Asian (SAS) AF: 0.00315 AC: 2 AN: 634

European-Finnish (FIN) AF: 0.0466 AC: 51 AN: 1094

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

European-Non Finnish (NFE) AF: 0.00257 AC: 47 AN: 18254

Other (OTH) AF: 0.0107 AC: 5 AN: 466

Alfa AF: 0.0119 Hom.: 45

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.085
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs751080433;

hg19: chrX-11272836;