rs5934997

chrX-11295613-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013427.3(ARHGAP6):c.589-40906A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 109,722 control chromosomes in the GnomAD database, including 5,216 homozygotes. There are 9,857 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (5216 hom., 9857 hem., cov: 21)
• Consequence: ARHGAP6 NM_013427.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMELX	NM_001142.2	c.54+771T>C		intron_variant		ENST00000380714.7
ARHGAP6	NM_013427.3	c.589-40906A>G		intron_variant		ENST00000337414.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP6	ENST00000337414.9	c.589-40906A>G		intron_variant		1	NM_013427.3	P2
AMELX	ENST00000380714.7	c.54+771T>C		intron_variant		1	NM_001142.2	P1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 35607 AN: 109668 Hom.: 5212 Cov.: 21 AF XY: 0.307 AC XY: 9816 AN XY: 31982

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.0234

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.374

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.325 AC: 35655 AN: 109722 Hom.: 5216 Cov.: 21 AF XY: 0.308 AC XY: 9857 AN XY: 32046

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.0238

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.296

Alfa AF: 0.310 Hom.: 2365

Bravo AF: 0.327

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	6.8
Dann	Benign	0.79

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: rs5934997; hg19: chrX-11313733;