19-48493993-C-A

Variant names:

• chr19-48493993-C-A
• rs1972279424
• NM_001388485.1:c.3793G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001388485.1(LMTK3):​c.3793G>T​(p.Ala1265Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 929,036 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: LMTK3 NM_001388485.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.712
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15757653).
• BS2: High AC in GnomAdExome4 at 15 AD gene.

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.3793G>T	p.Ala1265Ser	missense	Exon 12 of 15	NP_001375414.1	Q96Q04
	LMTK3	NM_001080434.2		c.3793G>T	p.Ala1265Ser	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.3793G>T	p.Ala1265Ser	missense	Exon 12 of 15	ENSP00000472020.1	Q96Q04
	LMTK3	ENST00000650440.1		c.3871G>T	p.Ala1291Ser	missense	Exon 13 of 16	ENSP00000497480.1	A0A3B3ISL5
	LMTK3	ENST00000673139.1		c.3793G>T	p.Ala1265Ser	missense	Exon 13 of 16	ENSP00000500153.1	Q96Q04

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000161 AC: 15 AN: 929036 Hom.: 0 Cov.: 30 AF XY: 0.0000114 AC XY: 5 AN XY: 438746

African (AFR) AF: 0.00 AC: 0 AN: 17776

American (AMR) AF: 0.00 AC: 0 AN: 3822

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7824

East Asian (EAS) AF: 0.00 AC: 0 AN: 9806

South Asian (SAS) AF: 0.00 AC: 0 AN: 18454

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9752

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2094

European-Non Finnish (NFE) AF: 0.0000181 AC: 15 AN: 826630

Other (OTH) AF: 0.00 AC: 0 AN: 32878

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.10
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.45	T
M_CAP	Pathogenic	0.81	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.71
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.061
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.63	T
Polyphen		0.012	B
Vest4		0.19
MutPred		0.20		Gain of glycosylation at A1265 (P = 0.0024)
MVP		0.37
ClinPred		0.46	T
GERP RS		-0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.3
Varity_R		0.080
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: rs1972279424; hg19: chr19-48997250;