Variant chr19-48494106-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001388485.1(LMTK3):c.3680G>A(p.Arg1227Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LMTK3
NM_001388485.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.984

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058548808).

BP6

Variant 19-48494106-C-T is Benign according to our data. Variant chr19-48494106-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2569373.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LMTK3	NM_001388485.1 linkuse as main transcript	c.3680G>A	p.Arg1227Lys	missense_variant	12/15	ENST00000600059.6
LMTK3	NM_001080434.2 linkuse as main transcript	c.3680G>A	p.Arg1227Lys	missense_variant	13/16
LMTK3	XM_011526411.3 linkuse as main transcript	c.3758G>A	p.Arg1253Lys	missense_variant	13/16
LMTK3	XM_011526412.3 linkuse as main transcript	c.3725G>A	p.Arg1242Lys	missense_variant	13/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMTK3	ENST00000600059.6 linkuse as main transcript	c.3680G>A	p.Arg1227Lys	missense_variant	12/15	2	NM_001388485.1	P2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1046854

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

494174

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000657

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

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:

0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.0022

T;.;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.28

T;T;T

M_CAP

Pathogenic

0.49

MetaRNN

Benign

0.059

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.81

N;.;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.10

.;N;.

REVEL

Benign

0.083

Sift

Benign

1.0

.;T;.

Sift4G

Benign

1.0

T;T;.

Polyphen

0.0

B;.;.

Vest4

0.12

MutPred

0.22

Gain of ubiquitination at R1227 (P = 0.0128);.;.;

MVP

0.26

ClinPred

0.17

GERP RS

1.7

Varity_R

0.057

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