11-18396874-A-G

Position:

• chr11-18396874-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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. 13/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.01

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2666773).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDHA	NM_005566.4	c.32A>G	p.Asn11Ser	missense_variant	2/8	ENST00000422447.8	NP_005557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDHA	ENST00000422447.8	c.32A>G	p.Asn11Ser	missense_variant	2/8	1	NM_005566.4	ENSP00000395337.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 10, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.61	D;.;.;.;T;.;.;.;.;D;D;.
Eigen	Benign	-0.10
Eigen_PC	Benign	0.037
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.61	.;T;T;T;T;T;T;T;T;.;T;T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.27	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.019	T
MutationAssessor	Benign	1.9	L;.;L;L;.;L;.;.;.;L;L;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.6	N;N;N;N;D;N;N;N;N;N;N;.
REVEL	Benign	0.25
Sift	Benign	0.17	T;T;T;T;T;T;T;T;T;T;T;.
Sift4G	Benign	0.34	T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0	B;.;.;.;.;.;.;.;.;B;B;.
Vest4		0.37
MutPred		0.26		Gain of disorder (P = 0.0897);Gain of disorder (P = 0.0897);Gain of disorder (P = 0.0897);Gain of disorder (P = 0.0897);Gain of disorder (P = 0.0897);Gain of disorder (P = 0.0897);Gain of disorder (P = 0.0897);Gain of disorder (P = 0.0897);.;Gain of disorder (P = 0.0897);Gain of disorder (P = 0.0897);Gain of disorder (P = 0.0897);
MVP		0.96
MPC		0.37
ClinPred		0.39	T
GERP RS		5.0
Varity_R		0.36
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-18418421;