rs782562759

Positions:

chrX-77656554-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000489.6(ATRX):c.4214+6A>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000549 in 1,202,038 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.000089 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000051 ( 0 hom. 13 hem. )

Consequence

ATRX
NM_000489.6 splice_donor_region, intron

Scores

Splicing: ADA: 0.00002471

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.127

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-77656554-T-C is Benign according to our data. Variant chrX-77656554-T-C is described in ClinVar as [Benign]. Clinvar id is 465060.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000893 (10/111969) while in subpopulation AMR AF= 0.000859 (9/10476). AF 95% confidence interval is 0.000448. There are 0 homozygotes in gnomad4. There are 1 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Hemizygotes in GnomAdExome4 at 13 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATRX	NM_000489.6 linkuse as main transcript	c.4214+6A>G		splice_donor_region_variant, intron_variant		ENST00000373344.11	NP_000480.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
ATRX	ENST00000373344.11 linkuse as main transcript	c.4214+6A>G	splice_donor_region_variant, intron_variant	1	NM_000489.6	ENSP00000362441	P3	P46100-1
ATRX	ENST00000395603.7 linkuse as main transcript	c.4100+6A>G	splice_donor_region_variant, intron_variant	1		ENSP00000378967	A2	P46100-4
ATRX	ENST00000624166.3 linkuse as main transcript	c.4010+6A>G	splice_donor_region_variant, intron_variant	1		ENSP00000485103
ATRX	ENST00000480283.5 linkuse as main transcript	c.*3842+6A>G	splice_donor_region_variant, intron_variant, NMD_transcript_variant	1		ENSP00000480196

Frequencies

GnomAD3 genomes

AF:

0.0000893

AC:

AN:

111969

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34135

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000859

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000235

AC:

AN:

182684

Hom.:

AF XY:

0.000149

AC XY:

AN XY:

67300

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00157

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000514

AC:

AN:

1090069

Hom.:

Cov.:

AF XY:

0.0000364

AC XY:

AN XY:

356767

show subpopulations

Gnomad4 AFR exome

AF:

0.0000762

Gnomad4 AMR exome

AF:

0.00145

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000120

Gnomad4 OTH exome

AF:

0.0000437

GnomAD4 genome

AF:

0.0000893

AC:

AN:

111969

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34135

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.000859

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000238

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Alpha thalassemia-X-linked intellectual disability syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.52

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000025

dbscSNV1_RF

Benign

0.0040

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

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