19-48494008-C-A

Position:

• chr19-48494008-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001388485.1(LMTK3):​c.3778G>T​(p.Ala1260Ser) 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. 13/19 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)
• Consequence: LMTK3 NM_001388485.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.214

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17540932).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMTK3	NM_001388485.1	c.3778G>T	p.Ala1260Ser	missense_variant	12/15	ENST00000600059.6
LMTK3	NM_001080434.2	c.3778G>T	p.Ala1260Ser	missense_variant	13/16
LMTK3	XM_011526411.3	c.3856G>T	p.Ala1286Ser	missense_variant	13/16
LMTK3	XM_011526412.3	c.3823G>T	p.Ala1275Ser	missense_variant	13/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMTK3	ENST00000600059.6	c.3778G>T	p.Ala1260Ser	missense_variant	12/15	2	NM_001388485.1	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2022

The c.3865G>T (p.A1289S) alteration is located in exon 13 (coding exon 13) of the LMTK3 gene. This alteration results from a G to T substitution at nucleotide position 3865, causing the alanine (A) at amino acid position 1289 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0038	T;.;.
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.43	T;T;T
M_CAP	Pathogenic	0.83	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.55	N;.;.
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.65	.;N;.
REVEL	Benign	0.080
Sift	Uncertain	0.0030	.;D;.
Sift4G	Benign	0.34	T;T;.
Polyphen		0.035	B;.;.
Vest4		0.26
MutPred		0.23		Gain of glycosylation at A1260 (P = 0.0019);.;.;
MVP		0.47
ClinPred		0.64	D
GERP RS		3.2
Varity_R		0.084

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-48997265;