Variant 19-48493819-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001388485.1(LMTK3):c.3967G>A(p.Ala1323Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000663 in 150,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LMTK3
NM_001388485.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.45

Variant links:

Genes affected

LMTK3 (HGNC:19295): (lemur tyrosine kinase 3) Predicted to enable protein kinase activity. Predicted to be involved in protein phosphorylation. Predicted to be located in Golgi membrane; axon; and dendrite. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LMTK3 links:

Genome browser will be placed here

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=0.30868366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMTK3	NM_001388485.1 linkuse as main transcript	c.3967G>A	p.Ala1323Thr	missense_variant	12/15	ENST00000600059.6	NP_001375414.1
LMTK3	NM_001080434.2 linkuse as main transcript	c.3967G>A	p.Ala1323Thr	missense_variant	13/16		NP_001073903.2
LMTK3	XM_011526411.3 linkuse as main transcript	c.4045G>A	p.Ala1349Thr	missense_variant	13/16		XP_011524713.1	A0A3B3ISL5
LMTK3	XM_011526412.3 linkuse as main transcript	c.4012G>A	p.Ala1338Thr	missense_variant	13/16		XP_011524714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMTK3	ENST00000600059.6 linkuse as main transcript	c.3967G>A	p.Ala1323Thr	missense_variant	12/15	2	NM_001388485.1	ENSP00000472020.1		Q96Q04

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150926

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000481

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1347688

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

664136

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000663

AC:

AN:

150926

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73648

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000481

Bravo

AF:

0.0000113

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

Oct 23, 2024

The c.4054G>A (p.A1352T) alteration is located in exon 13 (coding exon 13) of the LMTK3 gene. This alteration results from a G to A substitution at nucleotide position 4054, causing the alanine (A) at amino acid position 1352 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

Benign

0.085

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

T;.;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.52

T;T;T

M_CAP

Pathogenic

0.97

MetaRNN

Benign

0.31

T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.6

L;.;.

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-2.3

.;N;.

REVEL

Benign

0.28

Sift

Benign

0.031

.;D;.

Sift4G

Benign

0.076

T;T;.

Polyphen

0.099

B;.;.

Vest4

0.34

MutPred

0.17

Loss of loop (P = 0.0512);.;.;

MVP

0.51

ClinPred

0.83

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.084

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