rs11601413

Variant names:

• chr11-18400136-C-A
• rs11601413
• NM_005566.4:c.244+588C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005566.4(LDHA):​c.244+588C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 176,080 control chromosomes in the GnomAD database, including 1,231 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1080 hom., cov: 32)
  • Exomes 𝑓: 0.098 (151 hom.)
• Consequence: LDHA NM_005566.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196
• Publications: 13 publications found

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: PanelApp Australia, Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDHA	NM_005566.4	MANE Select	c.244+588C>A		intron	N/A	NP_005557.1
	LDHA	NM_001165414.2		c.331+588C>A		intron	N/A	NP_001158886.1
	LDHA	NM_001135239.2		c.244+588C>A		intron	N/A	NP_001128711.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDHA	ENST00000422447.8	TSL:1 MANE Select	c.244+588C>A		intron	N/A	ENSP00000395337.3
	LDHA	ENST00000542179.1	TSL:1	c.244+588C>A		intron	N/A	ENSP00000445331.1
	LDHA	ENST00000545215.5	TSL:1	n.127-701C>A		intron	N/A	ENSP00000442637.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17723 AN: 152098 Hom.: 1076 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.0552

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0891

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.0977 AC: 2331 AN: 23864 Hom.: 151 Cov.: 0 AF XY: 0.0960 AC XY: 1196 AN XY: 12460

African (AFR) AF: 0.0691 AC: 17 AN: 246

American (AMR) AF: 0.140 AC: 451 AN: 3214

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 34 AN: 300

East Asian (EAS) AF: 0.0418 AC: 72 AN: 1724

South Asian (SAS) AF: 0.0869 AC: 288 AN: 3314

European-Finnish (FIN) AF: 0.0809 AC: 50 AN: 618

Middle Eastern (MID) AF: 0.0806 AC: 5 AN: 62

European-Non Finnish (NFE) AF: 0.0978 AC: 1297 AN: 13266

Other (OTH) AF: 0.104 AC: 117 AN: 1120

GnomAD4 genome AF: 0.117 AC: 17742 AN: 152216 Hom.: 1080 Cov.: 32 AF XY: 0.115 AC XY: 8573 AN XY: 74430

African (AFR) AF: 0.113 AC: 4707 AN: 41528

American (AMR) AF: 0.153 AC: 2338 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 552 AN: 3470

East Asian (EAS) AF: 0.0546 AC: 283 AN: 5186

South Asian (SAS) AF: 0.104 AC: 502 AN: 4826

European-Finnish (FIN) AF: 0.0891 AC: 945 AN: 10604

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8008 AN: 68000

Other (OTH) AF: 0.123 AC: 261 AN: 2114

Alfa AF: 0.121 Hom.: 1410

Bravo AF: 0.120

Asia WGS AF: 0.117 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.9
DANN	Benign	0.55
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs11601413; hg19: chr11-18421683;