Variant chr19-48494043-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001388485.1(LMTK3):c.3743C>T(p.Pro1248Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000102 in 1,173,286 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000020 ( 0 hom. )

Consequence

LMTK3
NM_001388485.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.270

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20502415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LMTK3	NM_001388485.1 linkuse as main transcript	c.3743C>T	p.Pro1248Leu	missense_variant	12/15	ENST00000600059.6
LMTK3	NM_001080434.2 linkuse as main transcript	c.3743C>T	p.Pro1248Leu	missense_variant	13/16
LMTK3	XM_011526411.3 linkuse as main transcript	c.3821C>T	p.Pro1274Leu	missense_variant	13/16
LMTK3	XM_011526412.3 linkuse as main transcript	c.3788C>T	p.Pro1263Leu	missense_variant	13/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMTK3	ENST00000600059.6 linkuse as main transcript	c.3743C>T	p.Pro1248Leu	missense_variant	12/15	2	NM_001388485.1	P2

Frequencies

GnomAD3 genomes

AF:

0.0000662

AC:

AN:

151102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000527

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:

0.000964

GnomAD4 exome

AF:

0.00000196

AC:

AN:

1022184

Hom.:

Cov.:

AF XY:

0.00000207

AC XY:

AN XY:

482614

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000312

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:

0.0000662

AC:

AN:

151102

Hom.:

Cov.:

AF XY:

0.0000678

AC XY:

AN XY:

73764

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000527

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:

0.000964

Bravo

AF:

0.0000982

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 02, 2024

The c.3830C>T (p.P1277L) alteration is located in exon 13 (coding exon 13) of the LMTK3 gene. This alteration results from a C to T substitution at nucleotide position 3830, causing the proline (P) at amino acid position 1277 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

Benign

0.15

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0035

T;.;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.63

T;T;T

M_CAP

Pathogenic

0.95

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.81

L;.;.

MutationTaster

Benign

0.88

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-2.8

.;D;.

REVEL

Benign

0.19

Sift

Benign

0.067

.;T;.

Sift4G

Uncertain

0.021

D;D;.

Polyphen

0.99

D;.;.

Vest4

0.19

MutPred

0.19

Loss of relative solvent accessibility (P = 0.008);.;.;

MVP

0.31

ClinPred

0.66

GERP RS

2.0

Varity_R

0.074

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