chrX-77663467-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4BP6
The NM_000489.6(ATRX):āc.4035G>Cā(p.Leu1345Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000165 in 1,209,472 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L1345L) has been classified as Likely benign.
Frequency
Consequence
NM_000489.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATRX | NM_000489.6 | c.4035G>C | p.Leu1345Phe | missense_variant | 12/35 | ENST00000373344.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATRX | ENST00000373344.11 | c.4035G>C | p.Leu1345Phe | missense_variant | 12/35 | 1 | NM_000489.6 | P3 | |
ATRX | ENST00000395603.7 | c.3921G>C | p.Leu1307Phe | missense_variant | 11/34 | 1 | A2 | ||
ATRX | ENST00000624166.3 | c.3831G>C | p.Leu1277Phe | missense_variant | 12/14 | 1 | |||
ATRX | ENST00000480283.5 | c.*3663G>C | 3_prime_UTR_variant, NMD_transcript_variant | 13/36 | 1 |
Frequencies
GnomAD3 genomes AF: 0.00000893 AC: 1AN: 112041Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34201
GnomAD3 exomes AF: 0.00000546 AC: 1AN: 183244Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67758
GnomAD4 exome AF: 9.11e-7 AC: 1AN: 1097431Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 362799
GnomAD4 genome AF: 0.00000893 AC: 1AN: 112041Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34201
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 18, 2023 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Alpha thalassemia-X-linked intellectual disability syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at