chr19-48493953-C-T

Variant names:

• chr19-48493953-C-T
• rs776526950
• NM_001388485.1:c.3833G>A

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.3833G>A​(p.Gly1278Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000259 in 1,040,648 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: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: LMTK3 NM_001388485.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.237
• 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=0.14259467).
• BS2: High AC in GnomAd4 at 16 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.3833G>A	p.Gly1278Glu	missense	Exon 12 of 15	NP_001375414.1	Q96Q04
	LMTK3	NM_001080434.2		c.3833G>A	p.Gly1278Glu	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.3833G>A	p.Gly1278Glu	missense	Exon 12 of 15	ENSP00000472020.1	Q96Q04
	LMTK3	ENST00000650440.1		c.3911G>A	p.Gly1304Glu	missense	Exon 13 of 16	ENSP00000497480.1	A0A3B3ISL5
	LMTK3	ENST00000673139.1		c.3833G>A	p.Gly1278Glu	missense	Exon 13 of 16	ENSP00000500153.1	Q96Q04

Frequencies

GnomAD3 genomes AF: 0.000108 AC: 16 AN: 147894 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000269

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: 0.0000301

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000123 AC: 11 AN: 892754 Hom.: 0 Cov.: 30 AF XY: 0.00000951 AC XY: 4 AN XY: 420766

African (AFR) AF: 0.000119 AC: 2 AN: 16872

American (AMR) AF: 0.00 AC: 0 AN: 3254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6778

East Asian (EAS) AF: 0.00 AC: 0 AN: 5870

South Asian (SAS) AF: 0.00 AC: 0 AN: 18740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5706

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1918

European-Non Finnish (NFE) AF: 0.00000872 AC: 7 AN: 803136

Other (OTH) AF: 0.0000656 AC: 2 AN: 30480

GnomAD4 genome AF: 0.000108 AC: 16 AN: 147894 Hom.: 0 Cov.: 32 AF XY: 0.0000834 AC XY: 6 AN XY: 71984

African (AFR) AF: 0.000244 AC: 10 AN: 41006

American (AMR) AF: 0.000269 AC: 4 AN: 14880

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3394

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9050

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

European-Non Finnish (NFE) AF: 0.0000301 AC: 2 AN: 66342

Other (OTH) AF: 0.00 AC: 0 AN: 2038

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000136

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	0.17
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.50	T
M_CAP	Pathogenic	0.85	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.24
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	0.27	N
REVEL	Benign	0.15
Sift	Benign	0.034	D
Sift4G	Uncertain	0.037	D
Polyphen		0.075	B
Vest4		0.21
MutPred		0.12		Gain of solvent accessibility (P = 0.024)
MVP		0.40
ClinPred		0.22	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.11
Mutation Taster		=91/9	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: rs776526950; hg19: chr19-48997210;