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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_013427.3(ARHGAP6):c.589-12_589-10dupTTT 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 0.0048 ( 0 hom., 9 hem., cov: 19)

Exomes 𝑓: 0.00029 ( 0 hom. 1 hem. )

Consequence

ARHGAP6
NM_013427.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0850

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

AF:

0.00479

AC:

169

AN:

35278

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000608

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00156

Gnomad FIN

AF:

0.000908

Gnomad MID

AF:

0.0147

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.00438

GnomAD4 exome

AF:

0.000290

AC:

241

AN:

831868

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

241248

show subpopulations

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

African (AFR)

AF:

0.00239

AC:

AN:

18814

American (AMR)

AF:

0.000967

AC:

AN:

10339

Ashkenazi Jewish (ASJ)

AF:

0.000270

AC:

AN:

11124

East Asian (EAS)

AF:

0.0000915

AC:

AN:

21863

South Asian (SAS)

AF:

0.000927

AC:

AN:

19427

European-Finnish (FIN)

AF:

0.000227

AC:

AN:

22011

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2008

European-Non Finnish (NFE)

AF:

0.000204

AC:

141

AN:

691988

Other (OTH)

AF:

0.000496

AC:

AN:

34294

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.286

Heterozygous variant carriers

102

128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00482

AC:

170

AN:

35274

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

AN XY:

5872

show subpopulations

African (AFR)

AF:

0.0160

AC:

148

AN:

9247

American (AMR)

AF:

0.000608

AC:

AN:

3289

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

952

East Asian (EAS)

AF:

0.00

AC:

AN:

1101

South Asian (SAS)

AF:

0.00158

AC:

AN:

634

European-Finnish (FIN)

AF:

0.000908

AC:

AN:

1101

Middle Eastern (MID)

AF:

0.0161

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000823

AC:

AN:

18228

Other (OTH)

AF:

0.00429

AC:

AN:

466

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000399

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.085

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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X-11254716-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over