Variant chr11-18465640-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_144972.5(LDHAL6A):c.248A>G(p.Tyr83Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,236 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: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

LDHAL6A
NM_144972.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00

Variant links:

Genes affected

LDHAL6A (HGNC:28335): (lactate dehydrogenase A like 6A) Predicted to enable L-lactate dehydrogenase activity. Predicted to be involved in carbohydrate metabolic process and carboxylic acid metabolic process. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

LDHAL6A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.939

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDHAL6A	NM_144972.5 linkuse as main transcript	c.248A>G	p.Tyr83Cys	missense_variant	3/7	ENST00000280706.3	NP_659409.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDHAL6A	ENST00000280706.3 linkuse as main transcript	c.248A>G	p.Tyr83Cys	missense_variant	3/7	2	NM_144972.5	ENSP00000280706	P1
LDHAL6A	ENST00000396213.7 linkuse as main transcript	c.248A>G	p.Tyr83Cys	missense_variant	4/8	1		ENSP00000379516	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248218

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134174

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000297

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459236

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725940

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000227

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

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

Jan 09, 2024

The c.248A>G (p.Y83C) alteration is located in exon 3 (coding exon 3) of the LDHAL6A gene. This alteration results from a A to G substitution at nucleotide position 248, causing the tyrosine (Y) at amino acid position 83 to be replaced by a cysteine (C). 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

0.20

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Pathogenic

0.87

.;D;D

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.85

D;.;D

M_CAP

Benign

0.062

MetaRNN

Pathogenic

0.94

D;D;D

MetaSVM

Uncertain

0.38

MutationAssessor

Pathogenic

4.2

.;H;H

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-6.9

.;D;D

REVEL

Uncertain

0.55

Sift

Uncertain

0.0030

.;D;D

Sift4G

Uncertain

0.013

D;D;D

Polyphen

0.0040

.;B;B

Vest4

0.74

MutPred

0.77

Gain of catalytic residue at L84 (P = 0.0117);Gain of catalytic residue at L84 (P = 0.0117);Gain of catalytic residue at L84 (P = 0.0117);

MVP

0.93

MPC

0.52

ClinPred

0.66

GERP RS

1.4

Varity_R

0.48

gMVP

0.29

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over