NM_001388485.1:c.4153A>G

Variant names:

• chr19-48491479-T-C
• NM_001388485.1:c.4153A>G

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.4153A>G​(p.Thr1385Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1385M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (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: 0.995
• 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=0.12942171).

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.4153A>G	p.Thr1385Ala	missense	Exon 13 of 15	NP_001375414.1	Q96Q04
	LMTK3	NM_001080434.2		c.4153A>G	p.Thr1385Ala	missense	Exon 14 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.4153A>G	p.Thr1385Ala	missense	Exon 13 of 15	ENSP00000472020.1	Q96Q04
	LMTK3	ENST00000650440.1		c.4231A>G	p.Thr1411Ala	missense	Exon 14 of 16	ENSP00000497480.1	A0A3B3ISL5
	LMTK3	ENST00000673139.1		c.4153A>G	p.Thr1385Ala	missense	Exon 14 of 16	ENSP00000500153.1	Q96Q04

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1267554 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 619066

African (AFR) AF: 0.00 AC: 0 AN: 25274

American (AMR) AF: 0.00 AC: 0 AN: 15716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17702

East Asian (EAS) AF: 0.00 AC: 0 AN: 29654

South Asian (SAS) AF: 0.00 AC: 0 AN: 58226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4816

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1020188

Other (OTH) AF: 0.00 AC: 0 AN: 51616

GnomAD4 genome Cov.: 32

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	0.092
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Benign	0.91
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.33	N
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.13	T
PhyloP100		0.99
ClinPred		0.26	T
GERP RS		2.5
Varity_R		0.099
Mutation Taster		=96/4	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

hg19: chr19-48994736;