rs1992376
Variant summary
Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_005518.4(HMGCS2):c.858C>T(p.Ser286Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00788 in 1,613,814 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_005518.4 synonymous
Scores
Clinical Significance
Conservation
Publications
- 3-hydroxy-3-methylglutaryl-CoA synthase deficiencyInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, ClinGen, G2P
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ACMG classification
Our verdict: Benign. The variant received -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HMGCS2 | NM_005518.4 | c.858C>T | p.Ser286Ser | synonymous_variant | Exon 5 of 10 | ENST00000369406.8 | NP_005509.1 | |
HMGCS2 | NM_001166107.1 | c.732C>T | p.Ser244Ser | synonymous_variant | Exon 4 of 9 | NP_001159579.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HMGCS2 | ENST00000369406.8 | c.858C>T | p.Ser286Ser | synonymous_variant | Exon 5 of 10 | 1 | NM_005518.4 | ENSP00000358414.3 | ||
HMGCS2 | ENST00000544913.2 | c.732C>T | p.Ser244Ser | synonymous_variant | Exon 4 of 9 | 2 | ENSP00000439495.2 | |||
HMGCS2 | ENST00000472375.5 | n.305C>T | non_coding_transcript_exon_variant | Exon 2 of 3 | 5 | |||||
HMGCS2 | ENST00000476640.1 | n.589C>T | non_coding_transcript_exon_variant | Exon 3 of 4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00527 AC: 801AN: 152136Hom.: 2 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.00511 AC: 1282AN: 251084 AF XY: 0.00512 show subpopulations
GnomAD4 exome AF: 0.00815 AC: 11908AN: 1461560Hom.: 62 Cov.: 32 AF XY: 0.00797 AC XY: 5793AN XY: 727108 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00526 AC: 801AN: 152254Hom.: 2 Cov.: 33 AF XY: 0.00484 AC XY: 360AN XY: 74446 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
3-hydroxy-3-methylglutaryl-CoA synthase deficiency Benign:3
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This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
not provided Benign:2
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HMGCS2: BP4, BP7, BS2 -
not specified Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at