X-77635906-G-A
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.4699+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000619 in 1,194,751 control chromosomes in the GnomAD database, including 1 homozygotes. There are 33 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 0.000054 ( 0 hom., 1 hem., cov: 22)
Exomes 𝑓: 0.000063 ( 1 hom. 32 hem. )
Consequence
ATRX
NM_000489.6 intron
NM_000489.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0150
Publications
0 publications found
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 syndromeInheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
- ATR-X-related syndromeInheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
- intellectual disability-hypotonic facies syndrome, X-linked, 1Inheritance: XL Classification: MODERATE Submitted by: Ambry Genetics
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=-0.59).
BP6
Variant X-77635906-G-A is Benign according to our data. Variant chrX-77635906-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 434464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0000536 (6/111885) while in subpopulation SAS AF = 0.00149 (4/2688). AF 95% confidence interval is 0.000508. There are 0 homozygotes in GnomAd4. There are 1 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
BS2
High Hemizygotes in GnomAdExome4 at 32 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATRX | NM_000489.6 | c.4699+9C>T | intron_variant | Intron 16 of 34 | ENST00000373344.11 | NP_000480.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000537 AC: 6AN: 111830Hom.: 0 Cov.: 22 show subpopulations
GnomAD3 genomes
AF:
AC:
6
AN:
111830
Hom.:
Cov.:
22
Gnomad AFR
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GnomAD2 exomes AF: 0.0000877 AC: 15AN: 170952 AF XY: 0.0000692 show subpopulations
GnomAD2 exomes
AF:
AC:
15
AN:
170952
AF XY:
Gnomad AFR exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.0000628 AC: 68AN: 1082866Hom.: 1 Cov.: 28 AF XY: 0.0000911 AC XY: 32AN XY: 351440 show subpopulations
GnomAD4 exome
AF:
AC:
68
AN:
1082866
Hom.:
Cov.:
28
AF XY:
AC XY:
32
AN XY:
351440
show subpopulations
African (AFR)
AF:
AC:
0
AN:
25990
American (AMR)
AF:
AC:
0
AN:
34701
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19057
East Asian (EAS)
AF:
AC:
0
AN:
30108
South Asian (SAS)
AF:
AC:
65
AN:
53094
European-Finnish (FIN)
AF:
AC:
0
AN:
40203
Middle Eastern (MID)
AF:
AC:
0
AN:
3132
European-Non Finnish (NFE)
AF:
AC:
2
AN:
831117
Other (OTH)
AF:
AC:
1
AN:
45464
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.474
Heterozygous variant carriers
0
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4
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0.95
Allele balance
Age Distribution
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Age
GnomAD4 genome AF: 0.0000536 AC: 6AN: 111885Hom.: 0 Cov.: 22 AF XY: 0.0000293 AC XY: 1AN XY: 34083 show subpopulations
GnomAD4 genome
AF:
AC:
6
AN:
111885
Hom.:
Cov.:
22
AF XY:
AC XY:
1
AN XY:
34083
show subpopulations
African (AFR)
AF:
AC:
2
AN:
30791
American (AMR)
AF:
AC:
0
AN:
10619
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2646
East Asian (EAS)
AF:
AC:
0
AN:
3559
South Asian (SAS)
AF:
AC:
4
AN:
2688
European-Finnish (FIN)
AF:
AC:
0
AN:
6004
Middle Eastern (MID)
AF:
AC:
0
AN:
215
European-Non Finnish (NFE)
AF:
AC:
0
AN:
53147
Other (OTH)
AF:
AC:
0
AN:
1531
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.485
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
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0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
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Age
Alfa
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Bravo
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Apr 26, 2017
Genetic Services Laboratory, University of Chicago
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Alpha thalassemia-X-linked intellectual disability syndrome Benign:1
Feb 29, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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