Variant chr11-18429840-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The ENST00000541669.6(LDHC):c.348A>G(p.Ile116Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,348 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LDHC
ENST00000541669.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.06

Variant links:

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]

LDHC links:

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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;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.955

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDHC	NM_017448.5 linkuse as main transcript	c.348A>G	p.Ile116Met	missense_variant	4/8	ENST00000541669.6	NP_059144.1	P07864A0A140VKA7
LDHC	XM_047426934.1 linkuse as main transcript	c.-1A>G		5_prime_UTR_premature_start_codon_gain_variant	2/6		XP_047282890.1
LDHC	NM_002301.5 linkuse as main transcript	c.348A>G	p.Ile116Met	missense_variant	4/8		NP_002292.1	P07864A0A140VKA7
LDHC	XM_047426934.1 linkuse as main transcript	c.-1A>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 linkuse as main transcript	c.348A>G	p.Ile116Met	missense_variant	4/8	1	NM_017448.5	ENSP00000437783.1		P07864

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460348

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726562

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:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 23, 2023

The c.348A>G (p.I116M) alteration is located in exon 4 (coding exon 3) of the LDHC gene. This alteration results from a A to G substitution at nucleotide position 348, causing the isoleucine (I) at amino acid position 116 to be replaced by a methionine (M). 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

0.31

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.90

D;D;D;D;D;.

Eigen

Benign

0.11

Eigen_PC

Benign

-0.024

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.95

.;D;D;D;D;D

M_CAP

Pathogenic

0.32

MetaRNN

Pathogenic

0.95

D;D;D;D;D;D

MetaSVM

Pathogenic

0.81

MutationAssessor

Pathogenic

3.4

M;M;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.4

N;N;N;N;D;D

REVEL

Pathogenic

0.70

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Uncertain

0.023

D;D;D;D;D;D

Polyphen

0.94

P;P;.;.;D;.

Vest4

0.72

MutPred

0.76

Gain of MoRF binding (P = 0.0828);Gain of MoRF binding (P = 0.0828);.;Gain of MoRF binding (P = 0.0828);Gain of MoRF binding (P = 0.0828);Gain of MoRF binding (P = 0.0828);

MVP

0.95

MPC

0.46

ClinPred

0.99

GERP RS

2.8

Varity_R

0.71

gMVP

0.49

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over