Variant chr11-18477715-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_144972.5(LDHAL6A):c.806G>C(p.Arg269Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,459,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

LDHAL6A
NM_144972.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.71

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:

TSG101 (HGNC:15971): (tumor susceptibility 101) The protein encoded by this gene belongs to a group of apparently inactive homologs of ubiquitin-conjugating enzymes. The gene product contains a coiled-coil domain that interacts with stathmin, a cytosolic phosphoprotein implicated in tumorigenesis. The protein may play a role in cell growth and differentiation and act as a negative growth regulator. In vitro steady-state expression of this tumor susceptibility gene appears to be important for maintenance of genomic stability and cell cycle regulation. Mutations and alternative splicing in this gene occur in high frequency in breast cancer and suggest that defects occur during breast cancer tumorigenesis and/or progression. [provided by RefSeq, Jul 2008]

TSG101 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3350557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDHAL6A	NM_144972.5 linkuse as main transcript	c.806G>C	p.Arg269Thr	missense_variant	6/7	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.806G>C	p.Arg269Thr	missense_variant	6/7	2	NM_144972.5	ENSP00000280706	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

248260

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134218

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000549

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1459350

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

725932

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000452

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

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

Dec 28, 2022

The c.806G>C (p.R269T) alteration is located in exon 6 (coding exon 6) of the LDHAL6A gene. This alteration results from a G to C substitution at nucleotide position 806, causing the arginine (R) at amino acid position 269 to be replaced by a threonine (T). 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

Uncertain

0.44

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Uncertain

0.48

T;T

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.43

LIST_S2

Uncertain

0.91

.;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.34

T;T

MetaSVM

Benign

-0.59

MutationAssessor

Benign

2.0

M;M

MutationTaster

Benign

0.98

N;N;D

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.3

D;D

REVEL

Uncertain

0.33

Sift

Benign

0.057

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.99

D;D

Vest4

0.29

MVP

0.81

MPC

0.56

ClinPred

0.77

GERP RS

2.9

Varity_R

0.31

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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