1-220884433-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.1196G>A(p.Arg399His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000855 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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.1196G>A | p.Arg399His | missense_variant | 4/4 | ENST00000366903.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HLX | ENST00000366903.8 | c.1196G>A | p.Arg399His | missense_variant | 4/4 | 1 | NM_021958.4 | P1 | |
HLX | ENST00000427693.1 | c.395G>A | p.Arg132His | missense_variant | 4/4 | 3 | |||
HLX | ENST00000549319.2 | n.5003G>A | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152132Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000240 AC: 6AN: 249502Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135054
GnomAD4 exome AF: 0.0000917 AC: 134AN: 1461878Hom.: 0 Cov.: 33 AF XY: 0.0000908 AC XY: 66AN XY: 727244
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152132Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74314
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 25, 2022 | The c.1196G>A (p.R399H) 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 1196, causing the arginine (R) at amino acid position 399 to be replaced by a histidine (H). 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