19-48490583-G-A

Variant names:

• chr19-48490583-G-A
• rs8108419
• NM_001388485.1:c.4366+525C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001388485.1(LMTK3):​c.4366+525C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 149,626 control chromosomes in the GnomAD database, including 3,600 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3600 hom., cov: 30)
• Consequence: LMTK3 NM_001388485.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

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.4366+525C>T		intron	N/A	NP_001375414.1	Q96Q04
	LMTK3	NM_001080434.2		c.4366+525C>T		intron	N/A	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.4366+525C>T		intron	N/A	ENSP00000472020.1	Q96Q04
	LMTK3	ENST00000650440.1		c.4444+525C>T		intron	N/A	ENSP00000497480.1	A0A3B3ISL5
	LMTK3	ENST00000673139.1		c.4366+525C>T		intron	N/A	ENSP00000500153.1	Q96Q04

Frequencies

GnomAD3 genomes AF: 0.213 AC: 31821 AN: 149550 Hom.: 3600 Cov.: 30

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.216

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.224

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.213 AC: 31838 AN: 149626 Hom.: 3600 Cov.: 30 AF XY: 0.216 AC XY: 15756 AN XY: 72864

African (AFR) AF: 0.161 AC: 6506 AN: 40506

American (AMR) AF: 0.176 AC: 2638 AN: 15018

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1032 AN: 3460

East Asian (EAS) AF: 0.208 AC: 1050 AN: 5042

South Asian (SAS) AF: 0.322 AC: 1525 AN: 4734

European-Finnish (FIN) AF: 0.298 AC: 2966 AN: 9948

Middle Eastern (MID) AF: 0.226 AC: 65 AN: 288

European-Non Finnish (NFE) AF: 0.228 AC: 15424 AN: 67634

Other (OTH) AF: 0.226 AC: 472 AN: 2092

Alfa AF: 0.219 Hom.: 10459

Bravo AF: 0.201

Asia WGS AF: 0.243 AC: 846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.17
DANN	Benign	0.81
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs8108419; hg19: chr19-48993840;