Genetic Variant ARHGAP6:c.589-14_589-10delTTTTT (chrX-11254716-CAAAAA-C) – 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.589-14_589-10delTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 858,010 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., 9 hem., cov: 19)

Exomes 𝑓: 0.0013 ( 0 hom. 8 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

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.589-14_589-10delTTTTT	intron	N/A	NP_038286.2	O43182-1
ARHGAP6	NM_001287242.2		c.49-14_49-10delTTTTT	intron	N/A	NP_001274171.1
ARHGAP6	NM_013423.3		c.-21-14_-21-10delTTTTT	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.589-14_589-10delTTTTT	intron	N/A	ENSP00000338967.4	O43182-1
ARHGAP6	ENST00000303025.10	TSL:1	c.-21-14_-21-10delTTTTT	intron	N/A	ENSP00000302312.6	O43182-4
ARHGAP6	ENST00000380736.5	TSL:1	c.-21-14_-21-10delTTTTT	intron	N/A	ENSP00000370112.1	O43182-4

Frequencies

GnomAD3 genomes

AF:

0.00108

AC:

AN:

35322

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00304

Gnomad ASJ

AF:

0.0189

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000383

Gnomad OTH

AF:

0.00438

GnomAD2 exomes

AF:

0.0171

AC:

257

AN:

15013

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0167

Gnomad AMR exome

AF:

0.0147

Gnomad ASJ exome

AF:

0.0297

Gnomad EAS exome

AF:

0.0177

Gnomad FIN exome

AF:

0.00361

Gnomad NFE exome

AF:

0.0200

Gnomad OTH exome

AF:

0.0260

GnomAD4 exome

AF:

0.00130

AC:

1071

AN:

822692

Hom.:

AF XY:

0.0000338

AC XY:

AN XY:

236940

show subpopulations

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

African (AFR)

AF:

0.00193

AC:

AN:

18655

American (AMR)

AF:

0.00566

AC:

AN:

10074

Ashkenazi Jewish (ASJ)

AF:

0.00688

AC:

AN:

10905

East Asian (EAS)

AF:

0.00181

AC:

AN:

21503

South Asian (SAS)

AF:

0.00288

AC:

AN:

19117

European-Finnish (FIN)

AF:

0.00194

AC:

AN:

21658

Middle Eastern (MID)

AF:

0.00404

AC:

AN:

1982

European-Non Finnish (NFE)

AF:

0.00101

AC:

690

AN:

684881

Other (OTH)

AF:

0.00203

AC:

AN:

33917

⚠️ 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: 0.274

Heterozygous variant carriers

112

223

335

446

558

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00108

AC:

AN:

35318

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

AN XY:

5878

show subpopulations

African (AFR)

AF:

0.000108

AC:

AN:

9258

American (AMR)

AF:

0.00304

AC:

AN:

3290

Ashkenazi Jewish (ASJ)

AF:

0.0189

AC:

AN:

954

East Asian (EAS)

AF:

0.00

AC:

AN:

1101

South Asian (SAS)

AF:

0.00

AC:

AN:

634

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1101

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000383

AC:

AN:

18258

Other (OTH)

AF:

0.00429

AC:

AN:

466

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

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:

0.00

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

Publications

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X-11254716-CAAAAAAAAAAAA-CAAAAAAA

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