X-11294477-A-T

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.589-39770T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 110,652 control chromosomes in the GnomAD database, including 3,616 homozygotes. There are 9,053 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (3616 hom., 9053 hem., cov: 22)
• Consequence: ARHGAP6 NM_013427.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.06

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=-0.91).
• BP6: Variant X-11294477-A-T is Benign according to our data. Variant chrX-11294477-A-T is described in ClinVar as [Benign]. Clinvar id is 1249778.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMELX	NM_001142.2	c.-12-300A>T		intron_variant		ENST00000380714.7
ARHGAP6	NM_013427.3	c.589-39770T>A		intron_variant		ENST00000337414.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP6	ENST00000337414.9	c.589-39770T>A		intron_variant		1	NM_013427.3	P2
AMELX	ENST00000380714.7	c.-12-300A>T		intron_variant		1	NM_001142.2	P1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 31876 AN: 110598 Hom.: 3616 Cov.: 22 AF XY: 0.275 AC XY: 9031 AN XY: 32880

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.0572

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.0246

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.288 AC: 31898 AN: 110652 Hom.: 3616 Cov.: 22 AF XY: 0.275 AC XY: 9053 AN XY: 32944

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.0249

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.273

Alfa AF: 0.313 Hom.: 2002

Bravo AF: 0.280

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 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.15
Dann	Benign	0.52

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: rs5934996; hg19: chrX-11312597;