X-11296514-G-A

Position:

• chrX-11296514-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_013427.3(ARHGAP6):​c.589-41807C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 110,964 control chromosomes in the GnomAD database, including 1,802 homozygotes. There are 6,491 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (1802 hom., 6491 hem., cov: 22)
• Consequence: ARHGAP6 NM_013427.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.47

Genes affected

AMELX (HGNC:461): (amelogenin X-linked) This gene encodes a member of the amelogenin family of extracellular matrix proteins. Amelogenins are involved in biomineralization during tooth enamel development. Mutations in this gene cause X-linked amelogenesis imperfecta. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant X-11296514-G-A is Benign according to our data. Variant chrX-11296514-G-A is described in ClinVar as [Benign]. Clinvar id is 1276391.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMELX	NM_001142.2	c.55-265G>A		intron_variant		ENST00000380714.7
ARHGAP6	NM_013427.3	c.589-41807C>T		intron_variant		ENST00000337414.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP6	ENST00000337414.9	c.589-41807C>T		intron_variant		1	NM_013427.3	P2
AMELX	ENST00000380714.7	c.55-265G>A		intron_variant		1	NM_001142.2	P1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 22763 AN: 110912 Hom.: 1806 Cov.: 22 AF XY: 0.195 AC XY: 6469 AN XY: 33168

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.0453

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.0184

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.205 AC: 22783 AN: 110964 Hom.: 1802 Cov.: 22 AF XY: 0.195 AC XY: 6491 AN XY: 33230

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.0187

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.188

Alfa AF: 0.217 Hom.: 13935

Bravo AF: 0.194

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.3
DANN	Benign	0.38

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

Other links and lift over

dbSNP: rs5979395; hg19: chrX-11314634;