19-48493819-C-T

Variant names:

• chr19-48493819-C-T
• rs1390140326
• NM_001388485.1:c.3967G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001388485.1(LMTK3):​c.3967G>A​(p.Ala1323Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000663 in 150,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.45
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30868366).

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.3967G>A	p.Ala1323Thr	missense	Exon 12 of 15	NP_001375414.1	Q96Q04
	LMTK3	NM_001080434.2		c.3967G>A	p.Ala1323Thr	missense	Exon 13 of 16	NP_001073903.2	Q96Q04

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMTK3	ENST00000600059.6	TSL:2 MANE Select	c.3967G>A	p.Ala1323Thr	missense	Exon 12 of 15	ENSP00000472020.1	Q96Q04
	LMTK3	ENST00000650440.1		c.4045G>A	p.Ala1349Thr	missense	Exon 13 of 16	ENSP00000497480.1	A0A3B3ISL5
	LMTK3	ENST00000673139.1		c.3967G>A	p.Ala1323Thr	missense	Exon 13 of 16	ENSP00000500153.1	Q96Q04

Frequencies

GnomAD3 genomes AF: 0.00000663 AC: 1 AN: 150926 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.000481

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1347688 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 664136

African (AFR) AF: 0.00 AC: 0 AN: 27310

American (AMR) AF: 0.00 AC: 0 AN: 30988

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22944

East Asian (EAS) AF: 0.00 AC: 0 AN: 29914

South Asian (SAS) AF: 0.00 AC: 0 AN: 75354

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4184

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1056884

Other (OTH) AF: 0.00 AC: 0 AN: 55530

GnomAD4 genome AF: 0.00000663 AC: 1 AN: 150926 Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1 AN XY: 73648

African (AFR) AF: 0.00 AC: 0 AN: 41302

American (AMR) AF: 0.00 AC: 0 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10158

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67532

Other (OTH) AF: 0.000481 AC: 1 AN: 2080

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.52	T
M_CAP	Pathogenic	0.97	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.4
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.28
Sift	Benign	0.031	D
Sift4G	Benign	0.076	T
Polyphen		0.099	B
Vest4		0.34
MutPred		0.17		Loss of loop (P = 0.0512)
MVP		0.51
ClinPred		0.83	D
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.084
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs1390140326; hg19: chr19-48997076;