NM_001098272.3:c.890G>T

Variant names:

• chr5-43295767-C-A
• NM_001098272.3:c.890G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_001098272.3(HMGCS1):​c.890G>T​(p.Gly297Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HMGCS1 NM_001098272.3 missense
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 5.83

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 5-43295767-C-A is Pathogenic according to our data. Variant chr5-43295767-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 2580366.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGCS1	NM_001098272.3	c.890G>T	p.Gly297Val	missense_variant	Exon 6 of 11	ENST00000325110.11	NP_001091742.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMGCS1	ENST00000325110.11	c.890G>T	p.Gly297Val	missense_variant	Exon 6 of 11	1	NM_001098272.3	ENSP00000322706.6
HMGCS1	ENST00000433297.2	c.890G>T	p.Gly297Val	missense_variant	Exon 5 of 10	5		ENSP00000399402.2
HMGCS1	ENST00000514610.1	n.91G>T		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Rigid spine syndrome Pathogenic:1

Sep 20, 2023

Harry Perkins Institute Of Medical Research, University Of Western Australia

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Uncertain	0.70	D;D
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	.;D
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-5.2	D;D
REVEL	Uncertain	0.57
Sift	Benign	0.33	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.50	P;P
Vest4		0.58
MutPred		0.51		Loss of disorder (P = 0.0725);Loss of disorder (P = 0.0725);
MVP		0.64
MPC		1.4
ClinPred		0.80	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.69
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-43295869;