rs2106416

Variant names:

• chrX-11298622-C-T
• rs2106416
• NM_001142.2:c.219C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-11298622-C-T
• chrX-11298622-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001142.2(AMELX):​c.219C>T​(p.His73His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,207,173 control chromosomes in the GnomAD database, including 17,793 homozygotes. There are 79,614 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (2085 hom., 6593 hem., cov: 21)
  • Exomes 𝑓: 0.20 (15708 hom. 73021 hem.)
• Consequence: AMELX NM_001142.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.16
• Publications: 14 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant X-11298622-C-T is Benign according to our data. Variant chrX-11298622-C-T is described in ClinVar as Benign. ClinVar VariationId is 262997.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.16 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

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.219C>T	p.His73His	synonymous	Exon 5 of 6	NP_001133.1	Q99217-1
	ARHGAP6	NM_013427.3	MANE Select	c.589-43915G>A		intron	N/A	NP_038286.2	O43182-1
	AMELX	NM_182680.1		c.261C>T	p.His87His	synonymous	Exon 6 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.219C>T	p.His73His	synonymous	Exon 5 of 6	ENSP00000370090.3	Q99217-1
	AMELX	ENST00000380712.7	TSL:1	c.261C>T	p.His87His	synonymous	Exon 6 of 7	ENSP00000370088.3	Q99217-3
	ARHGAP6	ENST00000337414.9	TSL:1 MANE Select	c.589-43915G>A		intron	N/A	ENSP00000338967.4	O43182-1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 23971 AN: 109093 Hom.: 2083 Cov.: 21

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.0220

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.212

GnomAD2 exomes AF: 0.193 AC: 35383 AN: 183261 AF XY: 0.193

Gnomad AFR exome AF: 0.288

Gnomad AMR exome AF: 0.0984

Gnomad ASJ exome AF: 0.241

Gnomad EAS exome AF: 0.0243

Gnomad FIN exome AF: 0.289

Gnomad NFE exome AF: 0.219

Gnomad OTH exome AF: 0.208

GnomAD4 exome AF: 0.202 AC: 221584 AN: 1098028 Hom.: 15708 Cov.: 33 AF XY: 0.201 AC XY: 73021 AN XY: 363408

African (AFR) AF: 0.295 AC: 7783 AN: 26400

American (AMR) AF: 0.101 AC: 3565 AN: 35202

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 4696 AN: 19386

East Asian (EAS) AF: 0.0338 AC: 1022 AN: 30206

South Asian (SAS) AF: 0.175 AC: 9459 AN: 54147

European-Finnish (FIN) AF: 0.287 AC: 11580 AN: 40403

Middle Eastern (MID) AF: 0.265 AC: 1094 AN: 4134

European-Non Finnish (NFE) AF: 0.206 AC: 173250 AN: 842060

Other (OTH) AF: 0.198 AC: 9135 AN: 46090

GnomAD4 genome AF: 0.220 AC: 23994 AN: 109145 Hom.: 2085 Cov.: 21 AF XY: 0.209 AC XY: 6593 AN XY: 31515

African (AFR) AF: 0.280 AC: 8327 AN: 29757

American (AMR) AF: 0.134 AC: 1375 AN: 10284

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 628 AN: 2619

East Asian (EAS) AF: 0.0223 AC: 78 AN: 3490

South Asian (SAS) AF: 0.162 AC: 407 AN: 2520

European-Finnish (FIN) AF: 0.273 AC: 1549 AN: 5664

Middle Eastern (MID) AF: 0.310 AC: 67 AN: 216

European-Non Finnish (NFE) AF: 0.214 AC: 11235 AN: 52437

Other (OTH) AF: 0.210 AC: 311 AN: 1484

Alfa AF: 0.160 Hom.: 1235

Bravo AF: 0.212

EpiCase AF: 0.217

EpiControl AF: 0.213

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.4
DANN	Benign	0.83
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2106416; hg19: chrX-11316742; COSMIC: COSV61624192;