Variant 3-197512340-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_203314.3(BDH1):c.587T>C(p.Met196Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,392 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

BDH1
NM_203314.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.20

Variant links:

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]

BDH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.587T>C	p.Met196Thr	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 linkuse as main transcript	c.587T>C	p.Met196Thr	missense_variant	8/8	5	NM_203314.3	ENSP00000376184	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000415

AC:

AN:

240882

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131114

show subpopulations

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:

0.00000925

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1456392

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724400

show subpopulations

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2023

The c.587T>C (p.M196T) alteration is located in exon 8 (coding exon 6) of the BDH1 gene. This alteration results from a T to C substitution at nucleotide position 587, causing the methionine (M) at amino acid position 196 to be replaced by a threonine (T). 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

0.66

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.18

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Uncertain

0.65

D;D;D;T;.

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.97

M_CAP

Benign

0.074

MetaRNN

Uncertain

0.71

D;D;D;D;D

MetaSVM

Uncertain

-0.27

MutationAssessor

Benign

0.045

N;N;N;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.5

N;N;N;N;D

REVEL

Pathogenic

0.65

Sift

Benign

0.12

T;T;T;T;T

Sift4G

Benign

0.23

T;T;T;T;T

Polyphen

0.42

B;B;B;.;.

Vest4

0.64

MutPred

0.54

Gain of glycosylation at S195 (P = 0.0629);Gain of glycosylation at S195 (P = 0.0629);Gain of glycosylation at S195 (P = 0.0629);.;.;

MVP

0.94

MPC

0.59

ClinPred

0.60

GERP RS

5.3

Varity_R

0.32

gMVP

0.89

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over