NM_013427.3:c.589-161266A>G

Variant names:

• chrX-11415973-T-C
• rs5978435
• NM_013427.3:c.589-161266A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013427.3(ARHGAP6):​c.589-161266A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 111,185 control chromosomes in the GnomAD database, including 1,737 homozygotes. There are 6,496 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (1737 hom., 6496 hem., cov: 23)
• Consequence: ARHGAP6 NM_013427.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.734
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP6	NM_013427.3	MANE Select	c.589-161266A>G		intron	N/A	NP_038286.2
	ARHGAP6	NM_001287242.2		c.48+11575A>G		intron	N/A	NP_001274171.1
	ARHGAP6	NM_006125.3		c.589-161266A>G		intron	N/A	NP_006116.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP6	ENST00000337414.9	TSL:1 MANE Select	c.589-161266A>G		intron	N/A	ENSP00000338967.4
	ARHGAP6	ENST00000380736.5	TSL:1	c.-22+11575A>G		intron	N/A	ENSP00000370112.1
	ARHGAP6	ENST00000380718.1	TSL:1	c.589-161266A>G		intron	N/A	ENSP00000370094.1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 22183 AN: 111132 Hom.: 1740 Cov.: 23

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.0399

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.321

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.207

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.200 AC: 22186 AN: 111185 Hom.: 1737 Cov.: 23 AF XY: 0.194 AC XY: 6496 AN XY: 33419

African (AFR) AF: 0.145 AC: 4442 AN: 30624

American (AMR) AF: 0.133 AC: 1402 AN: 10529

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 695 AN: 2639

East Asian (EAS) AF: 0.0400 AC: 142 AN: 3548

South Asian (SAS) AF: 0.185 AC: 490 AN: 2652

European-Finnish (FIN) AF: 0.307 AC: 1817 AN: 5915

Middle Eastern (MID) AF: 0.342 AC: 75 AN: 219

European-Non Finnish (NFE) AF: 0.241 AC: 12745 AN: 52864

Other (OTH) AF: 0.204 AC: 309 AN: 1515

Alfa AF: 0.221 Hom.: 17118

Bravo AF: 0.184

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.1
DANN	Benign	0.63
PhyloP100		0.73
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5978435; hg19: chrX-11434093;