3-121634307-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_005335.6(HCLS1):c.803G>T(p.Arg268Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R268Q) 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.803G>T | p.Arg268Leu | missense_variant | 10/14 | ENST00000314583.8 | |
HCLS1 | NM_001292041.2 | c.692G>T | p.Arg231Leu | missense_variant | 9/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HCLS1 | ENST00000314583.8 | c.803G>T | p.Arg268Leu | missense_variant | 10/14 | 1 | NM_005335.6 | P1 | |
HCLS1 | ENST00000428394.6 | c.692G>T | p.Arg231Leu | missense_variant | 9/13 | 2 | |||
HCLS1 | ENST00000473883.5 | n.1606G>T | non_coding_transcript_exon_variant | 5/9 | 2 | ||||
HCLS1 | ENST00000495491.5 | c.*118G>T | 3_prime_UTR_variant, NMD_transcript_variant | 9/11 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251292Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135808
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 22, 2022 | The c.803G>T (p.R268L) alteration is located in exon 10 (coding exon 9) of the HCLS1 gene. This alteration results from a G to T substitution at nucleotide position 803, causing the arginine (R) at amino acid position 268 to be replaced by a leucine (L). 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