chrX-11294477-A-T

Variant names:

• chrX-11294477-A-T
• rs5934996
• NM_013427.3:c.589-39770T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

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]

AMELX Gene-Disease associations (from GenCC):

• amelogenesis imperfecta type 1E

  Inheritance: XL Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• amelogenesis imperfecta type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP6	NM_013427.3	MANE Select	c.589-39770T>A		intron	N/A	NP_038286.2	O43182-1
	AMELX	NM_001142.2	MANE Select	c.-12-300A>T		intron	N/A	NP_001133.1	Q99217-1
	ARHGAP6	NM_001287242.2		c.49-39770T>A		intron	N/A	NP_001274171.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP6	ENST00000337414.9	TSL:1 MANE Select	c.589-39770T>A		intron	N/A	ENSP00000338967.4	O43182-1
	AMELX	ENST00000380714.7	TSL:1 MANE Select	c.-12-300A>T		intron	N/A	ENSP00000370090.3	Q99217-1
	ARHGAP6	ENST00000380736.5	TSL:1	c.-21-39770T>A		intron	N/A	ENSP00000370112.1	O43182-4

Frequencies

GnomAD3 genomes AF: 0.288 AC: 31876 AN: 110598 Hom.: 3616 Cov.: 22

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

African (AFR) AF: 0.370 AC: 11233 AN: 30364

American (AMR) AF: 0.180 AC: 1876 AN: 10414

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 851 AN: 2639

East Asian (EAS) AF: 0.0249 AC: 89 AN: 3570

South Asian (SAS) AF: 0.223 AC: 580 AN: 2601

European-Finnish (FIN) AF: 0.321 AC: 1872 AN: 5825

Middle Eastern (MID) AF: 0.407 AC: 87 AN: 214

European-Non Finnish (NFE) AF: 0.281 AC: 14860 AN: 52836

Other (OTH) AF: 0.273 AC: 411 AN: 1507

Alfa AF: 0.313 Hom.: 2002

Bravo AF: 0.280

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.52
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5934996; hg19: chrX-11312597;