X-11295537-T-C

Position:

• chrX-11295537-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.589-40830A>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 110,548 control chromosomes in the GnomAD database, including 5,216 homozygotes. There are 10,168 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 0.33 (5216 hom., 10168 hem., cov: 22)
• Consequence: ARHGAP6 NM_013427.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.807

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMELX	NM_001142.2	c.54+695T>C		intron_variant		ENST00000380714.7	NP_001133.1
ARHGAP6	NM_013427.3	c.589-40830A>G		intron_variant		ENST00000337414.9	NP_038286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP6	ENST00000337414.9	c.589-40830A>G		intron_variant		1	NM_013427.3	ENSP00000338967	P2
AMELX	ENST00000380714.7	c.54+695T>C		intron_variant		1	NM_001142.2	ENSP00000370090	P1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 35928 AN: 110493 Hom.: 5213 Cov.: 22 AF XY: 0.309 AC XY: 10127 AN XY: 32739

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.0338

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.0246

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.371

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: 35974 AN: 110548 Hom.: 5216 Cov.: 22 AF XY: 0.310 AC XY: 10168 AN XY: 32804

Gnomad4 AFR AF: 0.556

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.0247

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.296

Alfa AF: 0.275 Hom.: 2013

Bravo AF: 0.327

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.0
DANN	Benign	0.73

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: rs5933871; hg19: chrX-11313657;