rs946252

Variant names:

• chrX-11294907-T-A
• rs946252
• NM_013427.3:c.589-40200A>T

Your query was ambiguous. Multiple possible variants found:

• chrX-11294907-T-A
• chrX-11294907-T-C
• chrX-11294907-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_013427.3(ARHGAP6):​c.589-40200A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: ARHGAP6 NM_013427.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 34 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP6	NM_013427.3	c.589-40200A>T		intron_variant	Intron 1 of 12	ENST00000337414.9	NP_038286.2
AMELX	NM_001142.2	c.54+65T>A		intron_variant	Intron 2 of 5	ENST00000380714.7	NP_001133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP6	ENST00000337414.9	c.589-40200A>T		intron_variant	Intron 1 of 12	1	NM_013427.3	ENSP00000338967.4
AMELX	ENST00000380714.7	c.54+65T>A		intron_variant	Intron 2 of 5	1	NM_001142.2	ENSP00000370090.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1033913 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 319539

African (AFR) AF: 0.00 AC: 0 AN: 25135

American (AMR) AF: 0.00 AC: 0 AN: 35094

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18985

East Asian (EAS) AF: 0.00 AC: 0 AN: 29925

South Asian (SAS) AF: 0.00 AC: 0 AN: 52623

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40473

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3985

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 783732

Other (OTH) AF: 0.00 AC: 0 AN: 43961

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 37895

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.91
DANN	Benign	0.46
PhyloP100		-1.2

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: rs946252; hg19: chrX-11313027;