chr1-23802472-A-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_000191.3(HMGCL):c.969T>C(p.Cys323=) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 33)
Consequence
HMGCL
NM_000191.3 synonymous
NM_000191.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.11
Genes affected
HMGCL (HGNC:5005): (3-hydroxy-3-methylglutaryl-CoA lyase) The protein encoded by this gene belongs to the HMG-CoA lyase family. It is a mitochondrial enzyme that catalyzes the final step of leucine degradation and plays a key role in ketone body formation. Mutations in this gene are associated with HMG-CoA lyase deficiency. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
Variant 1-23802472-A-G is Benign according to our data. Variant chr1-23802472-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1575691.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=3.11 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HMGCL | NM_000191.3 | c.969T>C | p.Cys323= | synonymous_variant | 9/9 | ENST00000374490.8 | |
HMGCL | NM_001166059.2 | c.756T>C | p.Cys252= | synonymous_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HMGCL | ENST00000374490.8 | c.969T>C | p.Cys323= | synonymous_variant | 9/9 | 1 | NM_000191.3 | P1 | |
HMGCL | ENST00000436439.6 | c.756T>C | p.Cys252= | synonymous_variant | 7/7 | 2 | |||
HMGCL | ENST00000235958.4 | c.540T>C | p.Cys180= | synonymous_variant | 5/5 | 5 | |||
HMGCL | ENST00000374487.6 | n.1566T>C | non_coding_transcript_exon_variant | 10/10 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Deficiency of hydroxymethylglutaryl-CoA lyase Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 21, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.