chr19-48491234-C-G

Position:

• chr19-48491234-C-G

Variant summary

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

The NM_001388485.1(LMTK3):​c.4240G>C​(p.Glu1414Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000796 in 1,255,568 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: LMTK3 NM_001388485.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.32

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMTK3	NM_001388485.1	c.4240G>C	p.Glu1414Gln	missense_variant	14/15	ENST00000600059.6
LMTK3	NM_001080434.2	c.4240G>C	p.Glu1414Gln	missense_variant	15/16
LMTK3	XM_011526411.3	c.4318G>C	p.Glu1440Gln	missense_variant	15/16
LMTK3	XM_011526412.3	c.4285G>C	p.Glu1429Gln	missense_variant	15/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMTK3	ENST00000600059.6	c.4240G>C	p.Glu1414Gln	missense_variant	14/15	2	NM_001388485.1	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.96e-7 AC: 1 AN: 1255568 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 612294

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.90e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Oct 12, 2021

The c.4327G>C (p.E1443Q) alteration is located in exon 15 (coding exon 15) of the LMTK3 gene. This alteration results from a G to C substitution at nucleotide position 4327, causing the glutamic acid (E) at amino acid position 1443 to be replaced by a glutamine (Q). 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	Uncertain	0.53
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T;.;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.63	T;T;T
M_CAP	Pathogenic	0.52	D
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Uncertain	0.35	D
MutationAssessor	Uncertain	2.3	M;.;.
MutationTaster	Benign	0.54	N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.8	.;N;.
REVEL	Uncertain	0.36
Sift	Uncertain	0.012	.;D;.
Sift4G	Uncertain	0.054	T;D;.
Polyphen		1.0	D;.;.
Vest4		0.64
MutPred		0.20		Gain of sheet (P = 0.0827);.;.;
MVP		0.80
ClinPred		0.92	D
GERP RS		3.1
Varity_R		0.15

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

LitVar

Other links and lift over

dbSNP: rs1198502196; hg19: chr19-48994491; COSMIC: COSV54315451;