19-48510834-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001388485.1(LMTK3):c.77-242A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 151,986 control chromosomes in the GnomAD database, including 6,176 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (6176 hom., cov: 32)
• Consequence: LMTK3 NM_001388485.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.711

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMTK3	NM_001388485.1	c.77-242A>G		intron_variant		ENST00000600059.6
LMTK3	NM_001080434.2	c.77-242A>G		intron_variant
LMTK3	XM_011526411.3	c.155-242A>G		intron_variant
LMTK3	XM_011526412.3	c.122-242A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMTK3	ENST00000600059.6	c.77-242A>G		intron_variant		2	NM_001388485.1	P2
LMTK3	ENST00000650440.1	c.155-242A>G		intron_variant				A2
LMTK3	ENST00000673139.1	c.77-242A>G		intron_variant				P2
LMTK3	ENST00000647709.2	c.77-242A>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32485 AN: 151868 Hom.: 6156 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.0925

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.0617

Gnomad OTH AF: 0.212

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.214 AC: 32549 AN: 151986 Hom.: 6176 Cov.: 32 AF XY: 0.220 AC XY: 16338 AN XY: 74278

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.0925

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.0617

Gnomad4 OTH AF: 0.209

Alfa AF: 0.0921 Hom.: 1463

Bravo AF: 0.231

Asia WGS AF: 0.354 AC: 1229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	1.0
Dann	Benign	0.27

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: rs9989661; hg19: chr19-49014091;