Genetic Variant NM_001388485.1:c.3959C>A (chr19-48493827-G-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001388485.1(LMTK3):c.3959C>A(p.Ala1320Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000284 in 1,338,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1320T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

LMTK3
NM_001388485.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.236

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1642721).

BS2

High AC in GnomAdExome4 at 38 AD gene.

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.3959C>A	p.Ala1320Glu	missense	Exon 12 of 15	NP_001375414.1	Q96Q04
	LMTK3	NM_001080434.2		c.3959C>A	p.Ala1320Glu	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.3959C>A	p.Ala1320Glu	missense	Exon 12 of 15	ENSP00000472020.1	Q96Q04
LMTK3	ENST00000650440.1		c.4037C>A	p.Ala1346Glu	missense	Exon 13 of 16	ENSP00000497480.1	A0A3B3ISL5
LMTK3	ENST00000673139.1		c.3959C>A	p.Ala1320Glu	missense	Exon 13 of 16	ENSP00000500153.1	Q96Q04

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

92218

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

AF:

0.0000284

AC:

AN:

1338150

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

659252

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26988

American (AMR)

AF:

0.00

AC:

AN:

29714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22446

East Asian (EAS)

AF:

0.00

AC:

AN:

29504

South Asian (SAS)

AF:

0.00

AC:

AN:

74222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43548

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4080

European-Non Finnish (NFE)

AF:

0.0000352

AC:

AN:

1052632

Other (OTH)

AF:

0.0000182

AC:

AN:

55016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0028

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.43

M_CAP

Pathogenic

0.95

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.4

PhyloP100

-0.24

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-0.61

REVEL

Benign

0.11

Sift

Benign

0.048

Sift4G

Benign

0.30

Polyphen

0.010

Vest4

0.40

MutPred

0.21

Gain of solvent accessibility (P = 0.005)

MVP

0.43

ClinPred

0.26

GERP RS

0.021

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.086

Mutation Taster

=93/7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over