X-11294907-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_013427.3(ARHGAP6):c.589-40200A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.73 (21299 hom., 23745 hem., cov: 23)
  • Exomes 𝑓: 0.69 (168091 hom. 222518 hem.)
  • Failed GnomAD Quality Control
• Consequence: ARHGAP6 NM_013427.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.18

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant X-11294907-T-C is Benign according to our data. Variant chrX-11294907-T-C is described in ClinVar as [Benign]. Clinvar id is 1281204.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 21296 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMELX	NM_001142.2	c.54+65T>C		intron_variant		ENST00000380714.7
ARHGAP6	NM_013427.3	c.589-40200A>G		intron_variant		ENST00000337414.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP6	ENST00000337414.9	c.589-40200A>G		intron_variant		1	NM_013427.3	P2
AMELX	ENST00000380714.7	c.54+65T>C		intron_variant		1	NM_001142.2	P1

Frequencies

GnomAD3 genomes AF: 0.732 AC: 80836 AN: 110443 Hom.: 21296 Cov.: 23 AF XY: 0.725 AC XY: 23689 AN XY: 32671

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.727

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.688 AC: 710833 AN: 1033278 Hom.: 168091 AF XY: 0.696 AC XY: 222518 AN XY: 319508

Gnomad4 AFR exome AF: 0.859

Gnomad4 AMR exome AF: 0.839

Gnomad4 ASJ exome AF: 0.664

Gnomad4 EAS exome AF: 0.616

Gnomad4 SAS exome AF: 0.571

Gnomad4 FIN exome AF: 0.669

Gnomad4 NFE exome AF: 0.688

Gnomad4 OTH exome AF: 0.680

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.732 AC: 80890 AN: 110505 Hom.: 21299 Cov.: 23 AF XY: 0.725 AC XY: 23745 AN XY: 32743

Gnomad4 AFR AF: 0.846

Gnomad4 AMR AF: 0.800

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.670

Gnomad4 NFE AF: 0.687

Gnomad4 OTH AF: 0.721

Alfa AF: 0.694 Hom.: 24066

Bravo AF: 0.750

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

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.0
Dann	Benign	0.56

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: rs946252; hg19: chrX-11313027; COSMIC: COSV61625132; COSMIC: COSV61625132;