rs141974120

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000489.6(ATRX):c.4239A>G(p.Glu1413Glu) variant causes a synonymous change. The variant allele was found at a frequency of 0.000215 in 1,208,759 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 74 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 0.0013 ( 0 hom., 43 hem., cov: 23)

Exomes 𝑓: 0.00011 ( 0 hom. 31 hem. )

Consequence

ATRX
NM_000489.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.72

Publications

0 publications found

Variant links:

Genes affected

ATRX (HGNC:886): (ATRX chromatin remodeler) The protein encoded by this gene contains an ATPase/helicase domain, and thus it belongs to the SWI/SNF family of chromatin remodeling proteins. This protein is found to undergo cell cycle-dependent phosphorylation, which regulates its nuclear matrix and chromatin association, and suggests its involvement in the gene regulation at interphase and chromosomal segregation in mitosis. Mutations in this gene are associated with X-linked syndromes exhibiting cognitive disabilities as well as alpha-thalassemia (ATRX) syndrome. These mutations have been shown to cause diverse changes in the pattern of DNA methylation, which may provide a link between chromatin remodeling, DNA methylation, and gene expression in developmental processes. Multiple alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2017]

ATRX Gene-Disease associations (from GenCC):

alpha thalassemia-X-linked intellectual disability syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
ATR-X-related syndrome
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
intellectual disability-hypotonic facies syndrome, X-linked, 1
Inheritance: XL Classification: MODERATE Submitted by: Ambry Genetics

ATRX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant X-77654176-T-C is Benign according to our data. Variant chrX-77654176-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 290043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00126 (142/112268) while in subpopulation AFR AF = 0.00435 (135/31050). AF 95% confidence interval is 0.00375. There are 0 homozygotes in GnomAd4. There are 43 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 43 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000489.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATRX	NM_000489.6	MANE Select	c.4239A>G	p.Glu1413Glu	synonymous	Exon 14 of 35	NP_000480.3
	ATRX	NM_138270.5		c.4125A>G	p.Glu1375Glu	synonymous	Exon 13 of 34	NP_612114.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ATRX	ENST00000373344.11	TSL:1 MANE Select	c.4239A>G	p.Glu1413Glu	synonymous	Exon 14 of 35	ENSP00000362441.4
ATRX	ENST00000395603.7	TSL:1	c.4125A>G	p.Glu1375Glu	synonymous	Exon 13 of 34	ENSP00000378967.3
ATRX	ENST00000624166.3	TSL:1	c.4035A>G	p.Glu1345Glu	synonymous	Exon 14 of 14	ENSP00000485103.1

Frequencies

GnomAD3 genomes

AF:

0.00127

AC:

142

AN:

112217

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00436

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000377

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:

0.00132

GnomAD2 exomes

AF:

0.000334

AC:

AN:

182453

AF XY:

0.000268

show subpopulations

Gnomad AFR exome

AF:

0.00365

Gnomad AMR exome

AF:

0.000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.000443

GnomAD4 exome

AF:

0.000108

AC:

118

AN:

1096491

Hom.:

Cov.:

AF XY:

0.0000856

AC XY:

AN XY:

362259

show subpopulations

African (AFR)

AF:

0.00330

AC:

AN:

26361

American (AMR)

AF:

0.000284

AC:

AN:

35197

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19359

East Asian (EAS)

AF:

0.00

AC:

AN:

30104

South Asian (SAS)

AF:

0.00

AC:

AN:

54104

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40158

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

0.00000832

AC:

AN:

841054

Other (OTH)

AF:

0.000304

AC:

AN:

46024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00126

AC:

142

AN:

112268

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

AN XY:

34480

show subpopulations

African (AFR)

AF:

0.00435

AC:

135

AN:

31050

American (AMR)

AF:

0.000377

AC:

AN:

10612

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3604

South Asian (SAS)

AF:

0.00

AC:

AN:

2734

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6107

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53079

Other (OTH)

AF:

0.00131

AC:

AN:

1531

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00130

Hom.:

Bravo

AF:

0.00135

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Alpha thalassemia-X-linked intellectual disability syndrome (1)

ATRX-related disorder (1)

Inborn genetic diseases (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.4

(source)

DANN

Benign

0.69

PhyloP100

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over