3-121631920-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_005335.6(HCLS1):āc.1387G>Cā(p.Glu463Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,614,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E463K) has been classified as Uncertain significance.
Frequency
Consequence
NM_005335.6 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 |
---|---|---|---|---|---|---|---|
HCLS1 | NM_005335.6 | c.1387G>C | p.Glu463Gln | missense_variant | 14/14 | ENST00000314583.8 | |
HCLS1 | NM_001292041.2 | c.1276G>C | p.Glu426Gln | missense_variant | 13/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HCLS1 | ENST00000314583.8 | c.1387G>C | p.Glu463Gln | missense_variant | 14/14 | 1 | NM_005335.6 | P1 | |
HCLS1 | ENST00000428394.6 | c.1276G>C | p.Glu426Gln | missense_variant | 13/13 | 2 | |||
HCLS1 | ENST00000473883.5 | n.2190G>C | non_coding_transcript_exon_variant | 9/9 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251278Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135800
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461856Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727222
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152318Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74464
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 14, 2023 | The c.1387G>C (p.E463Q) alteration is located in exon 14 (coding exon 13) of the HCLS1 gene. This alteration results from a G to C substitution at nucleotide position 1387, causing the glutamic acid (E) at amino acid position 463 to be replaced by a glutamine (Q). 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