19-48493827-G-A

Variant names:

• chr19-48493827-G-A
• rs1489950347
• NM_001388485.1:c.3959C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001388485.1(LMTK3):​c.3959C>T​(p.Ala1320Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000747 in 1,338,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1320T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: LMTK3 NM_001388485.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17311054).

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.3959C>T	p.Ala1320Val	missense	Exon 12 of 15	NP_001375414.1	Q96Q04
	LMTK3	NM_001080434.2		c.3959C>T	p.Ala1320Val	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.3959C>T	p.Ala1320Val	missense	Exon 12 of 15	ENSP00000472020.1	Q96Q04
	LMTK3	ENST00000650440.1		c.4037C>T	p.Ala1346Val	missense	Exon 13 of 16	ENSP00000497480.1	A0A3B3ISL5
	LMTK3	ENST00000673139.1		c.3959C>T	p.Ala1320Val	missense	Exon 13 of 16	ENSP00000500153.1	Q96Q04

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.47e-7 AC: 1 AN: 1338150 Hom.: 0 Cov.: 31 AF XY: 0.00000152 AC XY: 1 AN XY: 659252

African (AFR) AF: 0.00 AC: 0 AN: 26988

American (AMR) AF: 0.00 AC: 0 AN: 29714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22446

East Asian (EAS) AF: 0.00 AC: 0 AN: 29504

South Asian (SAS) AF: 0.00 AC: 0 AN: 74222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4080

European-Non Finnish (NFE) AF: 9.50e-7 AC: 1 AN: 1052632

Other (OTH) AF: 0.00 AC: 0 AN: 55016

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.53	T
M_CAP	Pathogenic	0.90	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.24
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.19
Sift	Benign	0.030	D
Sift4G	Benign	0.13	T
Polyphen		0.10	B
Vest4		0.35
MutPred		0.081		Loss of helix (P = 0.0558)
MVP		0.42
ClinPred		0.47	T
GERP RS		0.021
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.042
Mutation Taster		=95/5	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: rs1489950347; hg19: chr19-48997084;