chr1-220884477-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_021958.4(HLX):c.1240G>A(p.Ala414Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,614,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_021958.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HLX | NM_021958.4 | c.1240G>A | p.Ala414Thr | missense_variant | 4/4 | ENST00000366903.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HLX | ENST00000366903.8 | c.1240G>A | p.Ala414Thr | missense_variant | 4/4 | 1 | NM_021958.4 | P1 | |
HLX | ENST00000427693.1 | c.439G>A | p.Ala147Thr | missense_variant | 4/4 | 3 | |||
HLX | ENST00000549319.2 | n.5047G>A | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152206Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248756Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134780
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461796Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 727202
GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74358
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 30, 2024 | The c.1240G>A (p.A414T) alteration is located in exon 4 (coding exon 4) of the HLX gene. This alteration results from a G to A substitution at nucleotide position 1240, causing the alanine (A) at amino acid position 414 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at