rs667246

Variant names:

• chr1-119750744-T-A
• rs667246
• NM_005518.4:c.*5+53A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-119750744-T-A
• chr1-119750744-T-C
• chr1-119750744-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005518.4(HMGCS2):​c.*5+53A>T variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HMGCS2 NM_005518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438

Genes affected

HMGCS2 (HGNC:5008): (3-hydroxy-3-methylglutaryl-CoA synthase 2) The protein encoded by this gene belongs to the HMG-CoA synthase family. It is a mitochondrial enzyme that catalyzes the first reaction of ketogenesis, a metabolic pathway that provides lipid-derived energy for various organs during times of carbohydrate deprivation, such as fasting. Mutations in this gene are associated with HMG-CoA synthase deficiency. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGCS2	NM_005518.4	c.*5+53A>T		intron_variant	Intron 9 of 9	ENST00000369406.8	NP_005509.1
HMGCS2	NM_001166107.1	c.*5+53A>T		intron_variant	Intron 8 of 8		NP_001159579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMGCS2	ENST00000369406.8	c.*5+53A>T		intron_variant	Intron 9 of 9	1	NM_005518.4	ENSP00000358414.3
HMGCS2	ENST00000544913.2	c.*5+53A>T		intron_variant	Intron 8 of 8	2		ENSP00000439495.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 984232 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 509798

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.0
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs667246; hg19: chr1-120293367;