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:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_013427.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARHGAP6	NM_013427.3	MANE Select	c.589-12_589-10dupTTT	intron	N/A	NP_038286.2	O43182-1
ARHGAP6	NM_001287242.2		c.49-12_49-10dupTTT	intron	N/A	NP_001274171.1
ARHGAP6	NM_013423.3		c.-21-12_-21-10dupTTT	intron	N/A	NP_038267.1	O43182-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARHGAP6	ENST00000337414.9	TSL:1 MANE Select	c.589-10_589-9insTTT	intron	N/A	ENSP00000338967.4	O43182-1
ARHGAP6	ENST00000303025.10	TSL:1	c.-21-10_-21-9insTTT	intron	N/A	ENSP00000302312.6	O43182-4
ARHGAP6	ENST00000380736.5	TSL:1	c.-21-10_-21-9insTTT	intron	N/A	ENSP00000370112.1	O43182-4

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 v4.9

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

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over