11-18465777-C-T

Position:

• chr11-18465777-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_144972.5(LDHAL6A):​c.385C>T​(p.Pro129Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: LDHAL6A NM_144972.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.20

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]

ACMG classification

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, 0.938

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDHAL6A	NM_144972.5	c.385C>T	p.Pro129Ser	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.385C>T	p.Pro129Ser	missense_variant	3/7	2	NM_144972.5	ENSP00000280706.2
LDHAL6A	ENST00000396213.7	c.385C>T	p.Pro129Ser	missense_variant	4/8	1		ENSP00000379516.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Sep 08, 2024

The c.385C>T (p.P129S) alteration is located in exon 3 (coding exon 3) of the LDHAL6A gene. This alteration results from a C to T substitution at nucleotide position 385, causing the proline (P) at amino acid position 129 to be replaced by a serine (S). 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	0.25
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.80	.;D;D
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.037
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.98	D;.;D
M_CAP	Benign	0.070	D
MetaRNN	Pathogenic	0.94	D;D;D
MetaSVM	Pathogenic	0.83	D
MutationAssessor	Uncertain	2.7	.;M;M
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-6.4	.;D;D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0010	.;D;D
Sift4G	Benign	0.068	T;T;T
Polyphen		1.0	.;D;D
Vest4		0.48
MutPred		0.77		Loss of stability (P = 0.0777);Loss of stability (P = 0.0777);Loss of stability (P = 0.0777);
MVP		0.96
MPC		0.46
ClinPred		0.98	D
GERP RS		3.4
Varity_R		0.62
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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.

Other links and lift over

hg19: chr11-18487324;