rs1274662505

Variant names:

• chrX-11298259-C-T
• rs1274662505
• NM_001142.2:c.126C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001142.2(AMELX):​c.126C>T​(p.Tyr42Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,209,207 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000012 (0 hom. 4 hem.)
• Consequence: AMELX NM_001142.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.87
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant X-11298259-C-T is Benign according to our data. Variant chrX-11298259-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2659988.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.87 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 4 XL,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142.2. 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
	AMELX	NM_001142.2	MANE Select	c.126C>T	p.Tyr42Tyr	synonymous	Exon 4 of 6	NP_001133.1	Q99217-1
	ARHGAP6	NM_013427.3	MANE Select	c.589-43552G>A		intron	N/A	NP_038286.2	O43182-1
	AMELX	NM_182680.1		c.168C>T	p.Tyr56Tyr	synonymous	Exon 5 of 7	NP_872621.1	Q99217-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMELX	ENST00000380714.7	TSL:1 MANE Select	c.126C>T	p.Tyr42Tyr	synonymous	Exon 4 of 6	ENSP00000370090.3	Q99217-1
	AMELX	ENST00000380712.7	TSL:1	c.168C>T	p.Tyr56Tyr	synonymous	Exon 5 of 7	ENSP00000370088.3	Q99217-3
	ARHGAP6	ENST00000337414.9	TSL:1 MANE Select	c.589-43552G>A		intron	N/A	ENSP00000338967.4	O43182-1

Frequencies

GnomAD3 genomes AF: 0.00000895 AC: 1 AN: 111709 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000109 AC: 2 AN: 183446 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000244

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000118 AC: 13 AN: 1097498 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 4 AN XY: 362874

African (AFR) AF: 0.0000379 AC: 1 AN: 26390

American (AMR) AF: 0.00 AC: 0 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19378

East Asian (EAS) AF: 0.00 AC: 0 AN: 30192

South Asian (SAS) AF: 0.00 AC: 0 AN: 54132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4119

European-Non Finnish (NFE) AF: 0.0000119 AC: 10 AN: 841486

Other (OTH) AF: 0.0000434 AC: 2 AN: 46078

GnomAD4 genome AF: 0.00000895 AC: 1 AN: 111709 Hom.: 0 Cov.: 23 AF XY: 0.0000295 AC XY: 1 AN XY: 33887

African (AFR) AF: 0.00 AC: 0 AN: 30641

American (AMR) AF: 0.00 AC: 0 AN: 10584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.00 AC: 0 AN: 3584

South Asian (SAS) AF: 0.00 AC: 0 AN: 2654

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53097

Other (OTH) AF: 0.00 AC: 0 AN: 1506

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Likely 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	-0.55
CADD	Benign	7.1
DANN	Benign	0.76
PhyloP100		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1274662505; hg19: chrX-11316379;