11-18465640-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_144972.5(LDHAL6A):āc.248A>Gā(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 (ā ).
Frequency
Genomes: not found (cov: 31)
Exomes š: 6.9e-7 ( 0 hom. )
Consequence
LDHAL6A
NM_144972.5 missense
NM_144972.5 missense
Scores
4
8
7
Clinical Significance
Conservation
PhyloP100: 4.00
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]
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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 | 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 | c.248A>G | p.Tyr83Cys | missense_variant | 3/7 | 2 | NM_144972.5 | ENSP00000280706 | P1 | |
LDHAL6A | ENST00000396213.7 | c.248A>G | p.Tyr83Cys | missense_variant | 4/8 | 1 | ENSP00000379516 | P1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
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31
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248218Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134174
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GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459236Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 725940
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GnomAD4 genome Cov.: 31
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31
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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Pathogenic
.;D;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;.;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
.;H;H
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
.;D;D
REVEL
Uncertain
Sift
Uncertain
.;D;D
Sift4G
Uncertain
D;D;D
Polyphen
0.0040
.;B;B
Vest4
MutPred
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
MPC
0.52
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at