chr3-197512314-G-C

Position:

• chr3-197512314-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_203314.3(BDH1):​c.613C>G​(p.Arg205Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BDH1 NM_203314.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.70

Genes affected

BDH1 (HGNC:1027): (3-hydroxybutyrate dehydrogenase 1) This gene encodes a member of the short-chain dehydrogenase/reductase gene family. The encoded protein forms a homotetrameric lipid-requiring enzyme of the mitochondrial membrane and has a specific requirement for phosphatidylcholine for optimal enzymatic activity. The encoded protein catalyzes the interconversion of acetoacetate and (R)-3-hydroxybutyrate, the two major ketone bodies produced during fatty acid catabolism. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDH1	NM_203314.3	c.613C>G	p.Arg205Gly	missense_variant	8/8	ENST00000392379.6	NP_976059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDH1	ENST00000392379.6	c.613C>G	p.Arg205Gly	missense_variant	8/8	5	NM_203314.3	ENSP00000376184.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 19, 2024

The c.613C>G (p.R205G) alteration is located in exon 8 (coding exon 6) of the BDH1 gene. This alteration results from a C to G substitution at nucleotide position 613, causing the arginine (R) at amino acid position 205 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.70	D;D;D;T;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.069	D
MetaRNN	Uncertain	0.73	D;D;D;D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	0.22	N;N;N;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-4.1	D;D;D;D;D
REVEL	Uncertain	0.54
Sift	Benign	0.031	D;D;D;D;T
Sift4G	Benign	0.46	T;T;T;T;T
Polyphen		0.79	P;P;P;.;.
Vest4		0.76
MutPred		0.64		Loss of methylation at R205 (P = 0.027);Loss of methylation at R205 (P = 0.027);Loss of methylation at R205 (P = 0.027);.;.;
MVP		0.93
MPC		0.50
ClinPred		0.99	D
GERP RS		3.5
Varity_R		0.42
gMVP		0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-197239185;