Genetic Variant NM_005566.4:c.32A>G (chr11-18396874-A-G) – 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_005566.4(LDHA):c.32A>G(p.Asn11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

LDHA
NM_005566.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.01

Publications

0 publications found

Variant links:

Genes affected

LDHA (HGNC:6535): (lactate dehydrogenase A) This gene encodes the A subunit of lactate dehydrogenase enzyme which catalyzes the reversible conversion of pyruvate to lactate with the concomitant oxidation of NADH to NAD in anaerobic glycolysis. The protein is found predominantly in skeletal muscle and belongs to the lactate dehydrogenase family. Mutations in this gene have been linked to exertional myoglobinuria. The human genome contains several non-transcribed pseudogenes of this gene. [provided by RefSeq, Sep 2023]

LDHA Gene-Disease associations (from GenCC):

glycogen storage disease due to lactate dehydrogenase M-subunit deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet

LDHA 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=0.2666773).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005566.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LDHA	NM_005566.4	MANE Select	c.32A>G	p.Asn11Ser	missense	Exon 2 of 8	NP_005557.1	P00338-1
LDHA	NM_001165414.2		c.119A>G	p.Asn40Ser	missense	Exon 2 of 8	NP_001158886.1	P00338-3
LDHA	NM_001135239.2		c.32A>G	p.Asn11Ser	missense	Exon 2 of 7	NP_001128711.1	P00338-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LDHA	ENST00000422447.8	TSL:1 MANE Select	c.32A>G	p.Asn11Ser	missense	Exon 2 of 8	ENSP00000395337.3	P00338-1
LDHA	ENST00000542179.1	TSL:1	c.32A>G	p.Asn11Ser	missense	Exon 1 of 7	ENSP00000445331.1	P00338-1
LDHA	ENST00000545215.5	TSL:1	n.32A>G		non_coding_transcript_exon	Exon 2 of 7	ENSP00000442637.1	F5GWW2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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 M-subunit deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Uncertain

0.045

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.61

Eigen

Benign

-0.10

Eigen_PC

Benign

0.037

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.61

M_CAP

Benign

0.063

MetaRNN

Benign

0.27

MetaSVM

Uncertain

-0.019

MutationAssessor

Benign

1.9

PhyloP100

2.0

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.6

REVEL

Benign

0.25

Sift

Benign

0.17

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.37

MutPred

0.26

Gain of disorder (P = 0.0897)

MVP

0.96

MPC

0.37

ClinPred

0.39

GERP RS

5.0

PromoterAI

-0.024

Neutral

(source)

Varity_R

0.36

gMVP

0.15

Mutation Taster

=79/21

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

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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