Genetic Variant LIME1:p.Leu68Val (chr20-63737994-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017806.4(LIME1):c.202C>G(p.Leu68Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,418,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L68F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

LIME1
NM_017806.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.172

Publications

0 publications found

Variant links:

Genes affected

LIME1 (HGNC:26016): (Lck interacting transmembrane adaptor 1) This gene encodes a transmembrane adaptor protein that links the T and B-cell receptor stimulation to downstream signaling pathways via its association with the Src family kinases Lck and Lyn, respectively. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Mar 2015]

LIME1 links:

ENSG00000273154 (HGNC:):

ENSG00000273154 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12899122).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017806.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LIME1	NM_017806.4	MANE Select	c.202C>G	p.Leu68Val	missense	Exon 4 of 6	NP_060276.2	Q9H400-1
LIME1	NM_001305654.2		c.181-14C>G		intron	N/A	NP_001292583.1	A0A087WT39
LIME1	NM_001305655.2		c.181-14C>G		intron	N/A	NP_001292584.1	A0A087WT39

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LIME1	ENST00000309546.8	TSL:1 MANE Select	c.202C>G	p.Leu68Val	missense	Exon 4 of 6	ENSP00000309521.3	Q9H400-1
ENSG00000273154	ENST00000632538.1	TSL:3	c.520-14C>G		intron	N/A	ENSP00000488802.1	A0A0J9YYD9
LIME1	ENST00000899472.1		c.272C>G	p.Pro91Arg	missense	Exon 3 of 5	ENSP00000569531.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.05e-7

AC:

AN:

1418424

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

702686

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32302

American (AMR)

AF:

0.00

AC:

AN:

40650

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25484

East Asian (EAS)

AF:

0.00

AC:

AN:

37680

South Asian (SAS)

AF:

0.00

AC:

AN:

81762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42668

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

9.15e-7

AC:

AN:

1093440

Other (OTH)

AF:

0.00

AC:

AN:

58786

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.030

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.51

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.59

M_CAP

Benign

0.016

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

-0.17

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.0

REVEL

Benign

0.13

Sift

Benign

0.14

Sift4G

Benign

0.089

Polyphen

0.95

Vest4

0.17

MutPred

0.17

Gain of sheet (P = 0.0344)

MVP

0.42

MPC

1.0

ClinPred

0.38

GERP RS

2.3

PromoterAI

0.024

Neutral

(source)

Varity_R

0.11

gMVP

0.083

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over