Variant 4-99882008-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000499666.7(LAMTOR3):c.361G>T(p.Val121Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,451,586 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LAMTOR3
ENST00000499666.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.08

Variant links:

Genes affected

LAMTOR3 (HGNC:15606): (late endosomal/lysosomal adaptor, MAPK and MTOR activator 3) This gene encodes a scaffold protein that functions in the extracellular signal-regulated kinase (ERK) cascade. The protein is localized to late endosomes by the mitogen-activated protein-binding protein-interacting protein, and binds specifically to MAP kinase kinase MAP2K1/MEK1, MAP kinase MAPK3/ERK1, and MAP kinase MAPK1/ERK2. Studies of the orthologous gene in mouse indicate that it regulates late endosomal traffic and cell proliferation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. A pseudogene of this gene is located on the long arm of chromosome 13. [provided by RefSeq, Aug 2011]

LAMTOR3 links:

Genome browser will be placed here

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	Protein
LAMTOR3	NM_021970.4 linkuse as main transcript	c.361G>T	p.Val121Leu	missense_variant	7/7	ENST00000499666.7	NP_068805.1
LAMTOR3	NM_001243736.1 linkuse as main transcript	c.340G>T	p.Val114Leu	missense_variant	7/7		NP_001230665.1
LAMTOR3	NR_024170.1 linkuse as main transcript	n.564G>T		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMTOR3	ENST00000499666.7 linkuse as main transcript	c.361G>T	p.Val121Leu	missense_variant	7/7	1	NM_021970.4	ENSP00000424183	P1	Q9UHA4-1
LAMTOR3	ENST00000515100.1 linkuse as main transcript	n.446G>T		non_coding_transcript_exon_variant	6/6	1
LAMTOR3	ENST00000226522.8 linkuse as main transcript	c.340G>T	p.Val114Leu	missense_variant	7/7	3		ENSP00000226522		Q9UHA4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000413

AC:

AN:

241842

Hom.:

AF XY:

0.00000764

AC XY:

AN XY:

130910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000102

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:

0.00000138

AC:

AN:

1451586

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

722108

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000387

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

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 16, 2024

The c.361G>T (p.V121L) alteration is located in exon 7 (coding exon 6) of the LAMTOR3 gene. This alteration results from a G to T substitution at nucleotide position 361, causing the valine (V) at amino acid position 121 to be replaced by a leucine (L). 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

Pathogenic

0.90

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.070

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.049

T;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.64

D;D

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.9

N;N

REVEL

Pathogenic

0.66

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.017

D;D

Polyphen

0.19

B;.

Vest4

0.61

MutPred

0.57

Loss of sheet (P = 0.0181);.;

MVP

0.47

MPC

0.23

ClinPred

0.86

GERP RS

5.3

Varity_R

0.82

gMVP

0.50

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