chr19-48510834-T-C

Variant names:

• chr19-48510834-T-C
• rs9989661
• NM_001388485.1:c.77-242A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
LMTK3	NM_001388485.1	c.77-242A>G		intron_variant	Intron 1 of 14	ENST00000600059.6	NP_001375414.1
LMTK3	NM_001080434.2	c.77-242A>G		intron_variant	Intron 2 of 15		NP_001073903.2
LMTK3	XM_011526411.3	c.155-242A>G		intron_variant	Intron 2 of 15		XP_011524713.1
LMTK3	XM_011526412.3	c.122-242A>G		intron_variant	Intron 2 of 15		XP_011524714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMTK3	ENST00000600059.6	c.77-242A>G		intron_variant	Intron 1 of 14	2	NM_001388485.1	ENSP00000472020.1
LMTK3	ENST00000650440.1	c.155-242A>G		intron_variant	Intron 2 of 15			ENSP00000497480.1
LMTK3	ENST00000673139.1	c.77-242A>G		intron_variant	Intron 2 of 15			ENSP00000500153.1
LMTK3	ENST00000647709.2	n.77-242A>G		intron_variant	Intron 1 of 9			ENSP00000496937.2

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

African (AFR) AF: 0.477 AC: 19747 AN: 41406

American (AMR) AF: 0.186 AC: 2841 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0925 AC: 321 AN: 3470

East Asian (EAS) AF: 0.525 AC: 2700 AN: 5144

South Asian (SAS) AF: 0.171 AC: 826 AN: 4822

European-Finnish (FIN) AF: 0.122 AC: 1293 AN: 10572

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.0617 AC: 4192 AN: 67970

Other (OTH) AF: 0.209 AC: 442 AN: 2110

Alfa AF: 0.105 Hom.: 2610

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
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism (auto)

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: rs9989661; hg19: chr19-49014091;