19-48493911-G-A

Variant names:

• chr19-48493911-G-A
• rs1390969841
• NM_001388485.1:c.3875C>T

Variant summary

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

The NM_001388485.1(LMTK3):​c.3875C>T​(p.Ala1292Val) 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)
  • 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: -0.384

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=0.1245445).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMTK3	NM_001388485.1	c.3875C>T	p.Ala1292Val	missense_variant	Exon 12 of 15	ENST00000600059.6	NP_001375414.1
LMTK3	NM_001080434.2	c.3875C>T	p.Ala1292Val	missense_variant	Exon 13 of 16		NP_001073903.2
LMTK3	XM_011526411.3	c.3953C>T	p.Ala1318Val	missense_variant	Exon 13 of 16		XP_011524713.1
LMTK3	XM_011526412.3	c.3920C>T	p.Ala1307Val	missense_variant	Exon 13 of 16		XP_011524714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMTK3	ENST00000600059.6	c.3875C>T	p.Ala1292Val	missense_variant	Exon 12 of 15	2	NM_001388485.1	ENSP00000472020.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 881466 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 413682

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: 0.00

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

Jan 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3962C>T (p.A1321V) alteration is located in exon 13 (coding exon 13) of the LMTK3 gene. This alteration results from a C to T substitution at nucleotide position 3962, causing the alanine (A) at amino acid position 1321 to be replaced by a valine (V). 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	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0033	T;.;.
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.38	T;T;T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L;.;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.34	.;N;.
REVEL	Benign	0.064
Sift	Uncertain	0.027	.;D;.
Sift4G	Benign	0.37	T;T;.
Polyphen		0.023	B;.;.
Vest4		0.15
MutPred		0.24		Loss of helix (P = 0.1706);.;.;
MVP		0.43
ClinPred		0.27	T
GERP RS		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.057

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: rs1390969841; hg19: chr19-48997168;