Variant 11-18478707-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144972.5(LDHAL6A):c.836G>A(p.Gly279Asp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000551 in 1,451,024 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

LDHAL6A
NM_144972.5 missense, splice_region

Scores

Splicing: ADA: 0.0003118

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.85

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LDHAL6A	NM_144972.5 linkuse as main transcript	c.836G>A	p.Gly279Asp	missense_variant, splice_region_variant	7/7	ENST00000280706.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LDHAL6A	ENST00000280706.3 linkuse as main transcript	c.836G>A	p.Gly279Asp	missense_variant, splice_region_variant	7/7	2	NM_144972.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000412

AC:

AN:

242942

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131364

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000895

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000551

AC:

AN:

1451024

Hom.:

Cov.:

AF XY:

0.00000831

AC XY:

AN XY:

721996

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.00000271

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.57

D;D

Eigen

Benign

-0.0034

Eigen_PC

Benign

-0.059

FATHMM_MKL

Uncertain

0.93

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.74

D;D

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-5.7

D;D

REVEL

Uncertain

0.34

Sift

Benign

0.062

T;T

Sift4G

Benign

0.10

T;T

Polyphen

0.60

P;P

Vest4

0.15

MutPred

0.91

Gain of phosphorylation at Y281 (P = 0.0787);Gain of phosphorylation at Y281 (P = 0.0787);

MVP

0.83

MPC

0.15

ClinPred

0.95

GERP RS

2.4

Varity_R

0.55

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00031

dbscSNV1_RF

Benign

0.0080

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over