Variant chrX-11298622-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001142.2(AMELX):c.219C>T(p.His73=) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.16

Variant links:

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]

AMELX links:

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]

ARHGAP6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 262997.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-11298622-C-T is described in Lovd as [Likely_benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMELX	NM_001142.2 linkuse as main transcript	c.219C>T	p.His73=	synonymous_variant	5/6	ENST00000380714.7
ARHGAP6	NM_013427.3 linkuse as main transcript	c.589-43915G>A		intron_variant		ENST00000337414.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMELX	ENST00000380714.7 linkuse as main transcript	c.219C>T	p.His73=	synonymous_variant	5/6	1	NM_001142.2	P1	Q99217-1
ARHGAP6	ENST00000337414.9 linkuse as main transcript	c.589-43915G>A		intron_variant		1	NM_013427.3	P2	O43182-1

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

23971

AN:

109093

Hom.:

2083

Cov.:

AF XY:

0.209

AC XY:

6577

AN XY:

31453

show subpopulations

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

GnomAD3 exomes

AF:

0.193

AC:

35383

AN:

183261

Hom.:

2478

AF XY:

0.193

AC XY:

13063

AN XY:

67707

show subpopulations

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 SAS exome

AF:

0.172

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.:

AF XY:

0.201

AC XY:

73021

AN XY:

363408

show subpopulations

Gnomad4 AFR exome

AF:

0.295

Gnomad4 AMR exome

AF:

0.101

Gnomad4 ASJ exome

AF:

0.242

Gnomad4 EAS exome

AF:

0.0338

Gnomad4 SAS exome

AF:

0.175

Gnomad4 FIN exome

AF:

0.287

Gnomad4 NFE exome

AF:

0.206

Gnomad4 OTH exome

AF:

0.198

GnomAD4 genome

AF:

0.220

AC:

23994

AN:

109145

Hom.:

2085

Cov.:

AF XY:

0.209

AC XY:

6593

AN XY:

31515

show subpopulations

Gnomad4 AFR

AF:

0.280

Gnomad4 AMR

AF:

0.134

Gnomad4 ASJ

AF:

0.240

Gnomad4 EAS

AF:

0.0223

Gnomad4 SAS

AF:

0.162

Gnomad4 FIN

AF:

0.273

Gnomad4 NFE

AF:

0.214

Gnomad4 OTH

AF:

0.210

Alfa

AF:

0.160

Hom.:

1235

Bravo

AF:

0.212

EpiCase

AF:

0.217

EpiControl

AF:

0.213

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

4.4

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over