NM_203314.3:c.601G>A

Variant names:

• chr3-197512326-C-T
• NM_203314.3:c.601G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_203314.3(BDH1):​c.601G>A​(p.Ala201Thr) 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BDH1 NM_203314.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.06
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203314.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDH1	NM_203314.3	MANE Select	c.601G>A	p.Ala201Thr	missense	Exon 8 of 8	NP_976059.1
	BDH1	NM_004051.5		c.601G>A	p.Ala201Thr	missense	Exon 7 of 7	NP_004042.1
	BDH1	NM_203315.3		c.601G>A	p.Ala201Thr	missense	Exon 7 of 7	NP_976060.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDH1	ENST00000392379.6	TSL:5 MANE Select	c.601G>A	p.Ala201Thr	missense	Exon 8 of 8	ENSP00000376184.1
	BDH1	ENST00000392378.6	TSL:1	c.601G>A	p.Ala201Thr	missense	Exon 7 of 7	ENSP00000376183.2
	BDH1	ENST00000904000.1		c.640G>A	p.Ala214Thr	missense	Exon 7 of 7	ENSP00000574059.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1457994 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725356

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49808

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111844

Other (OTH) AF: 0.00 AC: 0 AN: 60350

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.52	D
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.070	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.0	L
PhyloP100		6.1
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.42
Sift	Benign	0.21	T
Sift4G	Benign	0.22	T
Polyphen		0.015	B
Vest4		0.18
MutPred		0.68		Gain of phosphorylation at A201 (P = 0.0514)
MVP		0.95
MPC		0.72
ClinPred		0.90	D
GERP RS		5.3
Varity_R		0.11
gMVP		0.85
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

hg19: chr3-197239197;