Genetic Variant ARHGAP6:c.589-12_589-10delTTT (chrX-11254716-CAAA-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP6_ModerateBS1

The NM_013427.3(ARHGAP6):c.589-12_589-10delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 809,472 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., 0 hem., cov: 19)

Exomes 𝑓: 0.011 ( 0 hom. 0 hem. )

Consequence

ARHGAP6
NM_013427.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0850

Variant links:

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]

ARHGAP6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant X-11254716-CAAA-C is Benign according to our data. Variant chrX-11254716-CAAA-C is described in ClinVar as [Benign]. Clinvar id is 402392.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0108 (8331/774153) while in subpopulation AMR AF= 0.0285 (272/9534). AF 95% confidence interval is 0.0257. There are 0 homozygotes in gnomad4_exome. There are 0 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP6	NM_013427.3 link	c.589-12_589-10delTTT		intron_variant	Intron 1 of 12	ENST00000337414.9	NP_038286.2	O43182-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP6	ENST00000337414.9 link	c.589-12_589-10delTTT		intron_variant	Intron 1 of 12	1	NM_013427.3	ENSP00000338967.4		O43182-1

Frequencies

GnomAD3 genomes

AF:

0.000170

AC:

AN:

35319

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

5875

show subpopulations

Gnomad AFR

AF:

0.000216

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000304

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00272

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0613

AC:

920

AN:

15013

Hom.:

AF XY:

0.00

AC XY:

AN XY:

991

show subpopulations

Gnomad AFR exome

AF:

0.0571

Gnomad AMR exome

AF:

0.0685

Gnomad ASJ exome

AF:

0.0531

Gnomad EAS exome

AF:

0.0546

Gnomad SAS exome

AF:

0.0699

Gnomad FIN exome

AF:

0.00902

Gnomad NFE exome

AF:

0.0795

Gnomad OTH exome

AF:

0.0442

GnomAD4 exome

AF:

0.0108

AC:

8331

AN:

774153

Hom.:

AF XY:

0.00

AC XY:

AN XY:

217783

show subpopulations

Gnomad4 AFR exome

AF:

0.0146

Gnomad4 AMR exome

AF:

0.0285

Gnomad4 ASJ exome

AF:

0.0150

Gnomad4 EAS exome

AF:

0.0139

Gnomad4 SAS exome

AF:

0.0151

Gnomad4 FIN exome

AF:

0.0146

Gnomad4 NFE exome

AF:

0.00988

Gnomad4 OTH exome

AF:

0.0127

GnomAD4 genome

AF:

0.000170

AC:

AN:

35319

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

5875

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.000304

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00272

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

X-11254716-CAAAAAAAAAAAA-CAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over