Genetic Variant LMTK3:p.Gly1278Ala (chr19-48493953-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001388485.1(LMTK3):c.3833G>C(p.Gly1278Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1278E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LMTK3
NM_001388485.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.237

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

LMTK3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18224227).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388485.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMTK3	NM_001388485.1	MANE Select	c.3833G>C	p.Gly1278Ala	missense	Exon 12 of 15	NP_001375414.1	Q96Q04
	LMTK3	NM_001080434.2		c.3833G>C	p.Gly1278Ala	missense	Exon 13 of 16	NP_001073903.2	Q96Q04

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LMTK3	ENST00000600059.6	TSL:2 MANE Select	c.3833G>C	p.Gly1278Ala	missense	Exon 12 of 15	ENSP00000472020.1	Q96Q04
LMTK3	ENST00000650440.1		c.3911G>C	p.Gly1304Ala	missense	Exon 13 of 16	ENSP00000497480.1	A0A3B3ISL5
LMTK3	ENST00000673139.1		c.3833G>C	p.Gly1278Ala	missense	Exon 13 of 16	ENSP00000500153.1	Q96Q04

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

5156

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

892754

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

420766

African (AFR)

AF:

0.00

AC:

AN:

16872

American (AMR)

AF:

0.00

AC:

AN:

3254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6778

East Asian (EAS)

AF:

0.00

AC:

AN:

5870

South Asian (SAS)

AF:

0.00

AC:

AN:

18740

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5706

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1918

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

803136

Other (OTH)

AF:

0.00

AC:

AN:

30480

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000433

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0047

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.54

M_CAP

Pathogenic

0.91

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.1

PhyloP100

-0.24

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.2

REVEL

Benign

0.21

Sift

Benign

0.046

Sift4G

Benign

0.39

Polyphen

0.46

Vest4

0.17

MutPred

0.11

Gain of helix (P = 0.0349)

MVP

0.45

ClinPred

0.16

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.099

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over