Variant X-77682471-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBA1

The NM_000489.6(ATRX):c.2785G>C(p.Glu929Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 110,313 control chromosomes in the GnomAD database, including 12,893 homozygotes. There are 16,657 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.52 ( 12893 hom., 16657 hem., cov: 22)

Exomes 𝑓: 0.67 ( 169861 hom. 241450 hem. )

Failed GnomAD Quality Control

Consequence

ATRX
NM_000489.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.280

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 -13 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ATRX. . Gene score misZ 3.1025 (greater than the threshold 3.09). GenCC has associacion of gene with alpha thalassemia-X-linked intellectual disability syndrome, ATR-X-related syndrome, intellectual disability-hypotonic facies syndrome, X-linked, 1.

BP4

Computational evidence support a benign effect (MetaRNN=0.006577015).

BP6

Variant X-77682471-C-G is Benign according to our data. Variant chrX-77682471-C-G is described in ClinVar as [Benign]. Clinvar id is 237852.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATRX	NM_000489.6 linkuse as main transcript	c.2785G>C	p.Glu929Gln	missense_variant	9/35	ENST00000373344.11	NP_000480.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATRX	ENST00000373344.11 linkuse as main transcript	c.2785G>C	p.Glu929Gln	missense_variant	9/35	1	NM_000489.6	ENSP00000362441	P3	P46100-1

Frequencies

GnomAD3 genomes

AF:

0.516

AC:

56915

AN:

110260

Hom.:

12906

Cov.:

AF XY:

0.511

AC XY:

16644

AN XY:

32556

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.743

Gnomad AMR

AF:

0.627

Gnomad ASJ

AF:

0.711

Gnomad EAS

AF:

0.528

Gnomad SAS

AF:

0.504

Gnomad FIN

AF:

0.681

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.685

Gnomad OTH

AF:

0.552

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.669

AC:

734383

AN:

1097922

Hom.:

169861

Cov.:

AF XY:

0.665

AC XY:

241450

AN XY:

363332

show subpopulations

Gnomad4 AFR exome

AF:

0.118

Gnomad4 AMR exome

AF:

0.736

Gnomad4 ASJ exome

AF:

0.696

Gnomad4 EAS exome

AF:

0.511

Gnomad4 SAS exome

AF:

0.496

Gnomad4 FIN exome

AF:

0.683

Gnomad4 NFE exome

AF:

0.701

Gnomad4 OTH exome

AF:

0.641

GnomAD4 genome

AF:

0.516

AC:

56903

AN:

110313

Hom.:

12893

Cov.:

AF XY:

0.511

AC XY:

16657

AN XY:

32619

show subpopulations

Gnomad4 AFR

AF:

0.132

Gnomad4 AMR

AF:

0.628

Gnomad4 ASJ

AF:

0.711

Gnomad4 EAS

AF:

0.528

Gnomad4 SAS

AF:

0.504

Gnomad4 FIN

AF:

0.681

Gnomad4 NFE

AF:

0.685

Gnomad4 OTH

AF:

0.551

Alfa

AF:

0.660

Hom.:

25457

Bravo

AF:

0.504

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_noAF

Benign

-0.93

CADD

Benign

DEOGEN2

Benign

0.021

.;.;T;T

LIST_S2

Benign

0.70

T;.;T;T

MetaRNN

Benign

0.0066

T;T;T;T

Sift4G

Benign

0.18

T;T;D;.

Vest4

0.10

gMVP

0.12

Splicing

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