rs56257144

Variant names:

• chr5-43294090-C-A
• rs56257144
• NM_001098272.3:c.1149G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-43294090-C-A
• chr5-43294090-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001098272.3(HMGCS1):​c.1149G>T​(p.Leu383Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000959 in 1,460,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L383L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: HMGCS1 NM_001098272.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660

Genes affected

HMGCS1 (HGNC:5007): (3-hydroxy-3-methylglutaryl-CoA synthase 1) Enables protein homodimerization activity. Predicted to be involved in acetyl-CoA metabolic process and farnesyl diphosphate biosynthetic process, mevalonate pathway. Predicted to be located in cytoplasm. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP7: Synonymous conserved (PhyloP=0.066 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGCS1	NM_001098272.3	c.1149G>T	p.Leu383Leu	synonymous_variant	Exon 8 of 11	ENST00000325110.11	NP_001091742.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMGCS1	ENST00000325110.11	c.1149G>T	p.Leu383Leu	synonymous_variant	Exon 8 of 11	1	NM_001098272.3	ENSP00000322706.6
HMGCS1	ENST00000433297.2	c.1149G>T	p.Leu383Leu	synonymous_variant	Exon 7 of 10	5		ENSP00000399402.2
HMGCS1	ENST00000508319.1	n.235G>T		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000199 AC: 5 AN: 251278 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135806

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000959 AC: 14 AN: 1460024 Hom.: 0 Cov.: 29 AF XY: 0.00000826 AC XY: 6 AN XY: 726454

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: 0.0000117

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	4.2
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs56257144; hg19: chr5-43294192;