Genetic Variant LDHB:p.Met281Ile (chr12-21635704-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_002300.8(LDHB):c.843G>A(p.Met281Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

LDHB
NM_002300.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.14

Publications

1 publications found

Variant links:

Genes affected

LDHB (HGNC:6541): (lactate dehydrogenase B) This gene encodes the B subunit of lactate dehydrogenase enzyme, which catalyzes the interconversion of pyruvate and lactate with concomitant interconversion of NADH and NAD+ in a post-glycolysis process. Alternatively spliced transcript variants have been found for this gene. Recent studies have shown that a C-terminally extended isoform is produced by use of an alternative in-frame translation termination codon via a stop codon readthrough mechanism, and that this isoform is localized in the peroxisomes. Mutations in this gene are associated with lactate dehydrogenase B deficiency. Pseudogenes have been identified on chromosomes X, 5 and 13. [provided by RefSeq, Feb 2016]

LDHB Gene-Disease associations (from GenCC):

glycogen storage disease due to lactate dehydrogenase H-subunit deficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LDHB links:

ENSG00000285854 (HGNC:):

ENSG00000285854 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.398761).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002300.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LDHB	NM_002300.8	MANE Select	c.843G>A	p.Met281Ile	missense	Exon 8 of 8	NP_002291.1	Q5U077
LDHB	NM_001315537.2		c.843G>A	p.Met281Ile	missense	Exon 8 of 8	NP_001302466.1	A0A5F9ZHM4
LDHB	NM_001174097.3		c.843G>A	p.Met281Ile	missense	Exon 8 of 8	NP_001167568.1	Q5U077

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LDHB	ENST00000350669.5	TSL:1 MANE Select	c.843G>A	p.Met281Ile	missense	Exon 8 of 8	ENSP00000229319.1	P07195
LDHB	ENST00000470985.3	TSL:1	n.316G>A		non_coding_transcript_exon	Exon 3 of 3
ENSG00000285854	ENST00000647960.1		n.837+1367G>A		intron	N/A	ENSP00000497202.1	A0A3B3IS95

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250666

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Glycogen storage disease due to lactate dehydrogenase H-subunit deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Uncertain

0.031

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.40

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.70

M_CAP

Benign

0.018

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.63

MutationAssessor

Benign

1.7

PhyloP100

6.1

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.1

REVEL

Benign

0.12

Sift

Benign

0.26

Sift4G

Benign

0.31

Polyphen

0.19

Vest4

0.51

MutPred

0.32

Gain of catalytic residue at M281 (P = 0)

MVP

0.76

MPC

0.33

ClinPred

0.85

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.65

gMVP

0.81

Mutation Taster

=54/46

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over