1-220884409-C-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_021958.4(HLX):c.1172C>A(p.Thr391Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,614,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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 Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HLX | NM_021958.4 | c.1172C>A | p.Thr391Lys | missense_variant | 4/4 | ENST00000366903.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HLX | ENST00000366903.8 | c.1172C>A | p.Thr391Lys | missense_variant | 4/4 | 1 | NM_021958.4 | P1 | |
HLX | ENST00000427693.1 | c.371C>A | p.Thr124Lys | missense_variant | 4/4 | 3 | |||
HLX | ENST00000549319.2 | n.4979C>A | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes AF: 0.000197 AC: 30AN: 152162Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249960Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135254
GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461872Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8AN XY: 727242
GnomAD4 genome AF: 0.000197 AC: 30AN: 152280Hom.: 0 Cov.: 33 AF XY: 0.000255 AC XY: 19AN XY: 74454
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 16, 2023 | The c.1172C>A (p.T391K) alteration is located in exon 4 (coding exon 4) of the HLX gene. This alteration results from a C to A substitution at nucleotide position 1172, causing the threonine (T) at amino acid position 391 to be replaced by a lysine (K). 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