Variant chr19-48485777-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001388485.1(LMTK3):c.4379A>G(p.Asn1460Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,610,500 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 0.000013 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

LMTK3
NM_001388485.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.13

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.063153505).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMTK3	NM_001388485.1 linkuse as main transcript	c.4379A>G	p.Asn1460Ser	missense_variant	15/15	ENST00000600059.6	NP_001375414.1
LMTK3	NM_001080434.2 linkuse as main transcript	c.4379A>G	p.Asn1460Ser	missense_variant	16/16		NP_001073903.2
LMTK3	XM_011526411.3 linkuse as main transcript	c.4457A>G	p.Asn1486Ser	missense_variant	16/16		XP_011524713.1	A0A3B3ISL5
LMTK3	XM_011526412.3 linkuse as main transcript	c.4424A>G	p.Asn1475Ser	missense_variant	16/16		XP_011524714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMTK3	ENST00000600059.6 linkuse as main transcript	c.4379A>G	p.Asn1460Ser	missense_variant	15/15	2	NM_001388485.1	ENSP00000472020.1		Q96Q04

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

GnomAD3 exomes

AF:

0.000121

AC:

AN:

240616

Hom.:

AF XY:

0.0000840

AC XY:

AN XY:

130942

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000740

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:

0.00

Gnomad OTH exome

AF:

0.000684

GnomAD4 exome

AF:

0.0000213

AC:

AN:

1458474

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

725336

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000656

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152026

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

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:

0.00

Bravo

AF:

0.0000642

ExAC

AF:

0.000132

AC:

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 16, 2024

The c.4466A>G (p.N1489S) alteration is located in exon 16 (coding exon 16) of the LMTK3 gene. This alteration results from a A to G substitution at nucleotide position 4466, causing the asparagine (N) at amino acid position 1489 to be replaced by a serine (S). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0028

T;.;.

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.54

T;T;T

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.063

T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.55

N;.;.

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.80

.;N;.

REVEL

Benign

0.27

Sift

Pathogenic

0.0

.;D;.

Sift4G

Pathogenic

0.0

D;D;.

Polyphen

0.96

P;.;.

Vest4

0.31

MutPred

0.16

Gain of phosphorylation at N1460 (P = 0.007);.;.;

MVP

0.32

ClinPred

0.14

GERP RS

3.2

Varity_R

0.11

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