rs118203895

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM5PP3_Moderate

The NM_002300.8(LDHB):​c.515G>A​(p.Arg172His) variant causes a missense change. The variant allele was found at a frequency of 0.0000093 in 1,613,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Affects (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R172P) has been classified as Likely pathogenic.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

LDHB
NM_002300.8 missense

Scores

5
12
2

Clinical Significance

Affects no assertion criteria provided O:1

Conservation

PhyloP100: 5.04
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chrnull-null-null-null is described in UniProt as null.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.899

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LDHBNM_002300.8 linkuse as main transcriptc.515G>A p.Arg172His missense_variant 5/8 ENST00000350669.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LDHBENST00000350669.5 linkuse as main transcriptc.515G>A p.Arg172His missense_variant 5/81 NM_002300.8 P1
LDHBENST00000673047.2 linkuse as main transcriptc.515G>A p.Arg172His missense_variant 5/8
LDHBENST00000396076.5 linkuse as main transcriptc.515G>A p.Arg172His missense_variant 5/85 P1
LDHBENST00000396075.5 linkuse as main transcriptc.515G>A p.Arg172His missense_variant 5/63

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151798
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461382
Hom.:
0
Cov.:
32
AF XY:
0.00000550
AC XY:
4
AN XY:
726980
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151798
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74138
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Affects
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Glycogen storage disease due to lactate dehydrogenase H-subunit deficiency Other:1
Affects, no assertion criteria providedliterature onlyOMIMMay 01, 1992- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.81
BayesDel_addAF
Pathogenic
0.34
D
BayesDel_noAF
Pathogenic
0.25
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.79
D;D;.
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.90
.;D;D
M_CAP
Benign
0.023
T
MetaRNN
Pathogenic
0.90
D;D;D
MetaSVM
Uncertain
-0.28
T
MutationAssessor
Pathogenic
3.6
H;H;.
MutationTaster
Benign
1.0
A;A
PrimateAI
Uncertain
0.78
T
PROVEAN
Uncertain
-4.1
D;D;D
REVEL
Uncertain
0.56
Sift
Uncertain
0.014
D;D;D
Sift4G
Uncertain
0.056
T;T;.
Polyphen
0.34
B;B;.
Vest4
0.62
MutPred
0.81
Gain of catalytic residue at S168 (P = 0);Gain of catalytic residue at S168 (P = 0);Gain of catalytic residue at S168 (P = 0);
MVP
0.86
MPC
0.36
ClinPred
0.97
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.53
gMVP
0.77

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.

Other links and lift over

dbSNP: rs118203895; hg19: chr12-21794966; API