Variant 19-48491222-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001388485.1(LMTK3):c.4252G>C(p.Asp1418His) variant causes a missense change. The variant allele was found at a frequency of 0.000000793 in 1,261,352 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.9e-7 ( 0 hom. )

Consequence

LMTK3
NM_001388485.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.05

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LMTK3	NM_001388485.1 linkuse as main transcript	c.4252G>C	p.Asp1418His	missense_variant	14/15	ENST00000600059.6
LMTK3	NM_001080434.2 linkuse as main transcript	c.4252G>C	p.Asp1418His	missense_variant	15/16
LMTK3	XM_011526411.3 linkuse as main transcript	c.4330G>C	p.Asp1444His	missense_variant	15/16
LMTK3	XM_011526412.3 linkuse as main transcript	c.4297G>C	p.Asp1433His	missense_variant	15/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMTK3	ENST00000600059.6 linkuse as main transcript	c.4252G>C	p.Asp1418His	missense_variant	14/15	2	NM_001388485.1	P2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000102

AC:

AN:

97914

Hom.:

AF XY:

0.00

AC XY:

AN XY:

55656

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000171

Gnomad SAS 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:

7.93e-7

AC:

AN:

1261352

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

615096

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000329

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

Cov.:

ExAC

AF:

0.0000173

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

Jul 14, 2023

The c.4339G>C (p.D1447H) alteration is located in exon 15 (coding exon 15) of the LMTK3 gene. This alteration results from a G to C substitution at nucleotide position 4339, causing the aspartic acid (D) at amino acid position 1447 to be replaced by a histidine (H). 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

Pathogenic

0.97

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.080

T;.;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.65

T;T;T

M_CAP

Pathogenic

0.68

MetaRNN

Uncertain

0.62

D;D;D

MetaSVM

Uncertain

0.015

MutationAssessor

Uncertain

2.7

M;.;.

MutationTaster

Benign

0.98

PrimateAI

Pathogenic

0.85

Sift4G

Uncertain

0.017

D;D;.

Polyphen

0.99

D;.;.

Vest4

0.73

MutPred

0.35

Gain of glycosylation at P1423 (P = 0.2101);.;.;

MVP

0.79

ClinPred

0.96

GERP RS

1.7

Varity_R

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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