11-18429752-C-G

Position:

• chr11-18429752-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000541669.6(LDHC):​c.260C>G​(p.Ala87Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LDHC ENST00000541669.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.19

Genes affected

LDHC (HGNC:6544): (lactate dehydrogenase C) Lactate dehydrogenase C catalyzes the conversion of L-lactate and NAD to pyruvate and NADH in the final step of anaerobic glycolysis. LDHC is testis-specific and belongs to the lactate dehydrogenase family. Two transcript variants have been detected which differ in the 5' untranslated region. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDHC	NM_017448.5	c.260C>G	p.Ala87Gly	missense_variant	4/8	ENST00000541669.6	NP_059144.1
LDHC	NM_002301.5	c.260C>G	p.Ala87Gly	missense_variant	4/8		NP_002292.1
LDHC	XM_047426934.1	c.-89C>G		5_prime_UTR_variant	2/6		XP_047282890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDHC	ENST00000541669.6	c.260C>G	p.Ala87Gly	missense_variant	4/8	1	NM_017448.5	ENSP00000437783.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.260C>G (p.A87G) alteration is located in exon 4 (coding exon 3) of the LDHC gene. This alteration results from a C to G substitution at nucleotide position 260, causing the alanine (A) at amino acid position 87 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.80	D;D;D;D;.
Eigen	Benign	0.11
Eigen_PC	Benign	-0.023
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.97	.;D;D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.58	D;D;D;D;D
MetaSVM	Uncertain	0.53	D
MutationAssessor	Uncertain	2.5	M;M;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.4	D;D;D;D;D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0010	D;D;T;D;D
Sift4G	Uncertain	0.028	D;D;D;D;D
Polyphen		0.80	P;P;.;P;.
Vest4		0.44
MutPred		0.60		Gain of disorder (P = 0.0715);Gain of disorder (P = 0.0715);Gain of disorder (P = 0.0715);Gain of disorder (P = 0.0715);Gain of disorder (P = 0.0715);
MVP		0.95
MPC		0.33
ClinPred		0.98	D
GERP RS		1.4
Varity_R		0.80
gMVP		0.13

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

Other links and lift over

dbSNP: rs1848231488; hg19: chr11-18451299;