chr6-55541742-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001042406.2(HMGCLL1):c.284G>T(p.Arg95Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000877 in 1,585,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R95T) has been classified as Uncertain significance.
Frequency
Consequence
NM_001042406.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HMGCLL1 | NM_001042406.2 | c.284G>T | p.Arg95Ile | missense_variant | 3/9 | ENST00000274901.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HMGCLL1 | ENST00000274901.9 | c.284G>T | p.Arg95Ile | missense_variant | 3/9 | 1 | NM_001042406.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152092Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000723 AC: 17AN: 235154Hom.: 0 AF XY: 0.0000863 AC XY: 11AN XY: 127492
GnomAD4 exome AF: 0.0000935 AC: 134AN: 1432860Hom.: 0 Cov.: 27 AF XY: 0.0000799 AC XY: 57AN XY: 713388
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74432
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 22, 2023 | The c.374G>T (p.R125I) alteration is located in exon 4 (coding exon 4) of the HMGCLL1 gene. This alteration results from a G to T substitution at nucleotide position 374, causing the arginine (R) at amino acid position 125 to be replaced by an isoleucine (I). 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